Lung structure disorders visualized by chest computed tomography in patients with pulmonary Langerhans cell histiocytosis and their correlation with the pulmonary function tests and disease extension

Lung structure disorders visualized by chest computed tomography in patients with pulmonary Langerhans cell histiocytosis and their correlation with the pulmonary function tests and disease extension | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Lung structure disorders visualized by chest computed tomography in patients with pulmonary Langerhans cell histiocytosis and their correlation with the pulmonary function tests and disease extension Maria Jeśkiewicz, Iwona Bestry, Małgorzata Sobiecka, Renata Langfort, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9357366/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Pulmonary Langerhans cell histiocytosis (PLCH) is characterized by the proliferation of cells affected by mutations in genes related to the mitogen-activated kinase pathway. The lungs can be involved as an isolated organ (IPLCH) or as one of the others (MS-PLCH). High-resolution computed tomography (HRCT) and pulmonary function tests play crucial roles in the diagnosis and assessment of its activity. This study aimed to evaluate radiological findings in PLCH patients and determine their correlation with the extent of the disease and pulmonary function. Material: This study evaluated 129 (53% women) PLCH patients, 96% of whom were smokers, with a mean age of 39.1 ± 14.1 years, who were hospitalized at the NTLDI in Warsaw between 2007 and 2021. Results: Cysts (89%), nodules (73%), emphysema (31%), reticular lesions (22%), cavitary nodules (21%), lymphadenopathy (16%), ground glass opacities (11%), dilatation of the pulmonary artery trunk (9%), bronchiectasis (7%), and honeycomb changes (1%) were visualized via HRCT. A negative correlation between the severity of cysts and nodules was found (p = 0.0002). A negative correlation between the intensity of the cysts and the FVC% pred. (p = 0.0029), FEV1% pred. (p < 0.0000), FEV1%/VC (p = 0.0001), and TLco (p < 0.0000) was shown. Higher intensity of smoking and greater severity of cysts classified patients as IPLCH with a 79.5% probability. Conclusions: Cysts, cavitary nodules, and nodules have been identified as the most frequent radiological findings in PLCH patients. The negative correlation between the severity of cysts and FVC% pred., FEV1% pred., and TLco% pred. was found. The higher severity of cysts and intensity of smoking discriminated patients with IPLCH from those with MS-PLCH. multisystem Langerhans cell histiocytosis isolated pulmonary Langerhans cell histiocytosis cystic lung diseases nodules cavitary nodules Introduction Pulmonary Langerhans cell histiocytosis (PLCH) is a rare disease characterized by the proliferation of Langerhans cells burdened with mutations in mitogen-stimulated kinase pathway genes accompanied by inflammation, which causes progressive destruction of the surrounding tissues [ 1 – 3 ]. The lungs may be involved as an isolated organ (IPLCH) or as one of many organs involved in a multisystem disease (MS-PLCH). The disease occurs predominantly in young adults, without sex predominance. Incidence rate of LCH is about 1/ million adults, with prevalence about 10/million [ 4 ]. Approximately 90–95% of PLCH patients are tobacco smokers, and 10–20% are marijuana smokers [ 1 – 3 , 5 – 9 ]. Radiological examinations are among the most important elements leading to diagnosis. Particularly noteworthy is high-resolution computed tomography (HRCT), which is often considered to be specific. The typical findings are centrilobular nodules (with a “tree-in-bud” appearance), cavitated nodules, and initially thick-walled cysts of various shapes. As the disease progresses, the cysts become larger and thin-walled with bizarre shapes. Lesions have a characteristic distribution with a predominance in the upper and middle parts of the lungs [ 1 – 3 , 5 – 11 ]. In PLCH patients, other radiological symptoms of smoking-related diseases are often visible (e.g., emphysematous bullae or ground glass opacities) [ 13 ]. Enlarged lymph nodes may be present in approximately 10% of affected patients. Signs of pulmonary hypertension and heart and pulmonary trunk enlargement are observed in patients with advanced disease [ 1 , 2 , 14 – 16 ]. The aim of this study was to investigate the correlation of disturbances in lung architecture visualized by chest CT with pulmonary function tests in patients with PLCH. Special attention was paid on differences in radiological picture between patients with isolated PLCH and those with multisystem disease with lung involvement. Materials The study included a retrospective evaluation of PLCH patients hospitalized at the Institute of Tuberculosis and Lung Diseases in Warsaw from 2007–2021 at the time of first presentation. During this period, the diagnosis of PLCH was established in 147 patients; however, owing to insufficient radiological documentation, 129 patients were analysed. Patients met the following criteria: the clinical and radiological findings were consistent with LCH, other diseases that could be the cause of the observed changes were excluded, and/or the diagnosis was confirmed by histological examination. Clinical data concerning age, sex, tobacco and marijuana smoking status, concomitant diseases, diagnostic delay, symptoms of the disease at the time of diagnosis, especially the presence of pneumothorax, the extent of the disease, and pulmonary function tests. Thoracic CT was assessed by experienced pulmonary radiologists (MJ, IB, KB, KO, BB). To determine the extent of the disease, laboratory tests, craniofacial CT, MRI of the brain and pituitary gland, PET/CT, bone scintigram, and ultrasound of the heart, abdominal cavity, and thyroid gland were performed, and changes in the bones or spinal cord were additionally confirmed by CT or magnetic resonance imaging tests dedicated to their assessment. The extent of the disease was determined according to the criteria proposed by the Histiocytosis Society [ 1 , 2 ]. The study was approved by the Internal Review Board of the National Tuberculosis and Lung Disease Institute No. 7.33/2018. The Ethics Committee of the National Tuberculosis and Lung Disease Institute approved this study (No. KB-11/2019). All patients provided written informed consent for the use of their medical records for research. Methods Pulmonary window CT (window parameters: W-1500; L-700) was used to qualitatively evaluate the presence of PLCH lesions, including nodules with disintegration, cysts, foci of shadowing with a ground-glass appearance, reticular lesions, emphysema, bronchial dilatation, and honeycomb lesions. Qualitative morphological evaluation of the lesions was performed in accordance with the Fleischner Society definitions [ 17 ]. The chest CT analysis utilized the assessment method outlined by Tazi et al. [ 18 ]. Each lung was divided into three fields: upper, middle, and lower. The upper field included the lung from the peak to the level of the tracheal bifurcation, the middle field from the tracheal bifurcation to the inferior pulmonary venous drainage, and the lower field below the level of the inferior pulmonary venous drainage to the level of the diaphragm. In addition, the supradiaphragmatic parts of the lungs were specified, dividing them into an anterior part, including the basal parts of the middle lobe and lingual lobe, and a posterior part, including the supradiaphragmatic parts of the basal segments of the lower lobes. Nodules were divided by size into nodules 10 mm. Nodules were quantitatively assessed on a four-point scale, depending on their percentage in each of the six lung fields (0–free lung field; 1–occupied 50%). The points from each lung field were then summed. The intensity of the nodules was determined as follows: low (0–6 points), medium (7–12 points), or high (13–18 points). The cysts were divided according to wall thickness into thin-walled cysts ( 2 mm). The above-described cystic lesions were quantitatively assessed on the four-grade scale described below according to their percentage in each of the six lung fields mentioned above (0- free lung field; 1- occupied 75%). The estimated points from each lung field were then summed. On this basis, the intensity of the cysts was classified as follows: low, 0–6 points; medium, 7–12 points; high, 13–18 points; and very high, 19–24 points. A CT cross-section of the chest containing the most severe lesions was selected for quantitative evaluation of each lung field. Owing to the characteristics of the disease, special attention was given to assessing the supradiaphragmatic parts of the lungs according to the following criteria: 1- supradiaphragmatic portions of the lungs; 2- free anterior supradiaphragmatic parts—free basal parts of the middle lobe and lingula; 3- free posterior supradiaphragmatic parts—free basal parts of the lower lobes; and 4- free anterior and posterior supradiaphragmatic parts—free basal parts of both the middle lobe and lingula as well as the lower lobes. Pulmonary function tests were performed according to the joint guidelines of the American Thoracic Society and the European Respiratory Society. The lung volume was measured via body plethysmography (MasterScreen software, ver. 4.65; Jeager, Wuerzburg, Germany), and the transfer factor of the lung for carbon monoxide (T LCO ) was determined via the single-breath technique [ 19 , 20 ]. The 6-min walk test (6MWT) was performed as recommended by the ATS [ 21 ]. Statistical methods . Statistical analyses were performed via the STATISTICA statistical package (data analysis software system), version 9.0, by StatSoft, Inc. (2009) ( www.statsoft.com ). Only nonparametric tests were used because the data did not meet the condition of normality of distributions. For the analysis of relationships between qualitative variables, contingency tables, and the chi-square test or one of its modifications, the chi-square test or the Yates test was used. The relationships between two quantitative variables were analysed via Spearman's rank correlation test. The relationships between the quantitative and qualitative variables were tested with the Mann‒Whitney test. The multivariate analysis used a combination of two methods from the field of pattern recognition, the k nearest neighbour rule (k-NS), the minus one element method and the chi-square test. The k-NS rule makes it possible to identify a group of patients based on knowledge of either the values of all features or a selected combination of them. All P values are two-sided and were considered to reflect a statistical significance of < 0.05. Results Study group A group of 129 patients (55% women) with PLCH was evaluated (Table 1 ). The mean age of the patients at diagnosis was 39.1 (± 14.1) years. Isolated PLCH (IPLCH) was diagnosed in 94 patients, and 35 patients had multisystem LCH with lung involvement (MS-PLCH). Nearly all patients were cigarette smokers (96%). Passive exposure to tobacco smoke was noted in 3 (2.5%) patients, and 2 (1.5%) patients had never smoked. The mean intensity of smoking was 18.5 ± 16.8 packs/year. Seventeen (13%) patients smoked marijuana. There were no differences between IPLCH and MS-PLCH according to age and gender; however, a significantly higher number of nonsmokers were noticed in MS-PLCH group than in IPLCH (1 vs.11%; p = 0.022). In addition, patients with MS-PLCH smoked fewer cigarettes than patients with IPLCH (12.3 ± 11.9 vs. 20.07 ± 17.7 pack/years; 0.007). Table 1 Characteristics of PLCH patients. Patients number All N (%) IPLCH N (%) MS-PLCH N (%) P 129 94(73) 35(27) Gender 0.330 Women 68 (53) 52(55) 16(46) Men 61 (47) 42(45) 19(54) Smokers 124 (96) 93(99) 31(89) 0.987 Non-smokers 5 (4) 1(1) 4(11) 0.022 Marijuana users 17 (13%) 13(14) 4(11) 0.947 Smoking pack/years (mean ± SD) 18.5 ± 16,8 20.07 ± 17.7 12.3 ± 11.9 0.007 Age (mean ± SD) 39.1 ± 14,1 40 ± 14.1 36.14.2 0.15 Histology Presence of CD1a and/or CD207 90 (70%) 61(65) 29(83) 0.04 Stellar scars 17 (13%) 14(15) 3(9) 0.34 BAL > 5% CD1a positive 3 (2%) 3(3) 0 Diagnosis based on clinical and radiological picture 19 (15%) 16(17) 3(9) 0.2 MS-PLCH 35 (27) 35 (100) Pituitary gland 16 (12.4) 16 (46) Facial bones 15 (11.6) 15 (43) Cranial bones 13 (10) 13 (37) Brain 5 (3.9) 5 (14) Skin 4 (3) 4 (11) Gingiva 3 (2) 3 (11) Liver 2 (1.5) 2 (6) 0ther 4 (3) 4 (11) BAL, bronchoalveolar lavage IPLCH, isolated pulmonary Langerhans cell histiocytosis MS-PLCH, multisystem Langerhans cell histiocytosis with lung involvement PLCH, pulmonary Langerhans cell histiocytosis SD- standard deviation A definite diagnosis based on the characteristic microscopy image and the expression of the CD1a and/or CD207 antigen was established in 90 (70%) patients. In 17 (13%) patients, histological examination revealed the evolution of histiocytic lesions with the formation of stellar-shaped scars. The presence of > 5% CD1a-positive cells in the bronchoalveolar lavage fluid was detected in 3 (2%) patients. Characteristic clinical and radiological findings and the exclusion of other causes of the disease were the basis of diagnosis in 19 (15%) patients. More frequently, CD1a and CD207 positive cells were detected in patients with MS-PLCH than in IPLCH ( 83 vs. 65%; p = 0.004). Among the 35 patients with MS-PLCH the most commonly involved organs were the pituitary gland, facial bones, skull bones, skin, brain, liver, mucous membranes and other bones (spine, ribs, femurs and hip bone) in: 16 (46%), 15 (43%), 13 (37%), 4(11%), 5(14%), 2(6%), 3 (9%) and in 4 (11%) patients respectively. MS-PLCH with involvement of high-risk organs was diagnosed in seven (20%) patients. The frequencies of symptoms and concomitant diseases are shown in Table 2 . Table 2 Concomitant diseases and symptoms in PLCH patients Concomitant diseases All N (%) IPLCH N (%) MS-PLCH N (%) P GERD 35 (27) 23 (24) 12 (34) 0.428 COPD 31 (24) 23 (24) 8 (23) 0.967 Obesity 30 (23) 19 (20) 11 (31) 0.180 Arterial hypertension 27 (21) 17 (18) 10 (29) 0.289 Thyroid diseases 15 (11) 8 (9) 7 (20) 0.133 Asthma 9 (7) 7 (7) 2 (6) 0.964 Diabetes 8 (6) 7 (7) 1 (3) 0.446 Autoimmune diseases 8 (6) 3 (3) 5 (14) 0.055 Coronary artery disease 7 (5) 5 (5) 2 (6) 0.727 Cholecystolithiasis 5 (4) 4 (4) 1 (3) 0.874 Hypoxemic respiratory failure 4 (3) 3 (3) 1 (3) 0.628 Respiratory failure 1 (1) 1 (1) 0 NS Depression 2 (2) 2 (2) 0 NS Myoma uteri 3 (2) 3 (3) 0 NS Cancer 5 (4) 3 (3) 2 (6) 0.208 Alcohol abuse 9 (7) 8 (9) 1 (3) 0.464 Clinical symptoms Cough 92 (71) 67 (71) 25 (71) 0.839 Decreased exercise tolerance 83 (64) 59 (62) 24 (69) 0.685 Dyspnoea 75 (58) 55 (59) 20 (57) 0.516 Sputum 31 (24) 23 (24) 8 (23) 0.976 Loss of weight 38 (29) 30 (32) 8 (23) 0.431 Sweats 7 (5) 4 (4) 3 (9) 0.599 Fever 7 (5) 6 (6) 1 (3) 0.673 Bone pain 10 (8) 2 (2) 8 (23) 0.0004 Pneumothorax 35(27) 17(18) 18 (51) 0.0002 COPD, chronic obstructive pulmonary disease GERD, gastroesophageal reflux disease Patients with multisystem disease had similar pulmonary symptoms to those with isolated PLCH, but more frequently experienced bone pains (23 vs 2%; p = 0.0004) and pneumothorax ( 51 vs 18%; p = 0.0002) than IPLCH patients. Patients with IPLCH had a similar profile of comorbidities as patients with MS-PLCH. Analysis of radiological lesions The lesions found on HRCT were cysts in 115 (89%), nodules in 95 (73%), emphysema in 40 (31%) patients, reticular lesions in 28 (22%) patients, cavitary nodules in 27 (21%) patients, and ground glass opacities in 14 (11%) patients. Bronchial dilatation and honeycomb-like lesions were relatively rarely observed, in 9 (7%) patients and 1(1%) patient, respectively (Table 3 ). Table 3 Characteristics of lesions detected by computed tomography in PLCH patients Patients number All N (%) IPLCH N (%) MS-PLCH N (%) p 129 94(73) 35(27) Nodules 10 mm 3 (2) 2(2) 1(3) 0.807 Cavitated nodules 27 (21) 21(22) 6(17) 0.519 Thin-walled cysts 115 (89) 84(89) 31(89) 0.9 Thick-walled cysts 55 (43) 39(41) 16(46) 0.666 Lacunar cysts 78 (60) 54(57) 24(69) 0.197 Emphysema 40 (31) 28(30) 12(35) 0.623 Reticular lesions 28 (22) 20(21) 8(23) 0.847 Ground glass opacities 14 (11) 10 (11) 4 (11) 0.898 Bronchiectasis 9 (7) 8 (9) 1 (3) 0.262 Honeycombing changes 1 (1) 1 (1) Hilar and mediastinal lymphadenopathy 21 (16) 14 (15) 7 (20) 0.664 Mediastinal lymphadenopathy 9 (7) 6 (6) 3(9) 0.992 Hilar lymphadenopathy 12 (9) 8 (9) 4 (11) 0.612 Pulmonary artery truncus > 30 mm 11 (9) 8(9) 3(9) 0.991 Mean intensity of nodules 4,4 ± 3,4 4.5 ± 3.5 3.9 ± 3.3 0.257 Intensity of nodules Low 95 (74) 67 (71) 28 (80) 0.317 Median 31 (24) 24 (25) 7 (20) 0.513 High 3 (2) 3(3) 0 Mean intensity of cysts 11,9 ± 6,7 11.3 ± 6.8 13.4 ± 6.3 0.098 Intensity of cysts Low 33 (26) 29 (31) 4 (11) 0.025 Median 38 (29) 28 (30) 10 (29) 0.893 High 33 (26) 18 (20) 14 (40) 0.023 Very high 25 (19) 18 (19) 7 (20) 0.931 Assessment of supradiaphragmatic parts Lesions in supradiaphragmatic parts 34 (26) 20 (21) 14 (40) 0.033 Without lesions in basal parts of meddle lobe and lingula 24 (19) 20 (21) 4 (11) 0.203 Without lesions in basal parts of lower lobes 7 (5) 5 (5) 2 (6) 0.727 Without lesions in basal parts of meddle lobe, lingula and lower lobes 64 (50) 49 (52) 15 (42) 0.349 IPLCH, isolated pulmonary Langerhans cell histiocytosis MS-PLCH, multisystem Langerhans cell histiocytosis with lung involvement Table 3 Nodules 10 mm in diameter were detected in 31 (24%) and 3 (2%) patients, respectively. Thin-walled cysts were the most common morphological lesions and were visualized in 115 (89%) patients. Thick-walled cysts and sinusoidal cysts were detected in 55 (43%) and 78 (60%) patients, respectively. The mean intensity of the nodules was 4.4 (± 3.4). In 95 (74%) patients, the intensity of the nodules was low, medium in 31 (24%) patients, and high in 3 (2%) patients. The intensity of the cysts was as follows: small, medium, high, and very high in 33 (26%), 38 (29%), 33 (26%), and 25 (19%) patients, respectively. The mean score of the cysts was 11.9 (± 6.7). A negative correlation was found between the intensity of the cysts and the intensity of the nodules (R=-0.319; p = 0.0002). Widening of the pulmonary artery trunk > 30 mm was demonstrated in 11 (9%) patients. Hilar and mediastinal lymphadenopathy was detected in 21 (16%) patients. The hilar lymph nodes were enlarged in 12 (9%) patients, whereas the mediastinal lymph nodes were enlarged in 9 (7%) patients. The most common lesion-free parts of the supradiaphragmatic lungs were both anterior and posterior, that is, the basal parts of the middle lobe and uvula and the basal parts of the lower lobes at the same time. This pattern of distribution was observed in 64 (50%) patients. In addition, quite often, only the anterior parts were free of lesions in 24 (19%) patients, and only the posterior portions of the lung base were free in only 7 (5%) patients. In 34 (26%) patients, the supradiaphragmatic parts of the lungs were involved in the disease process. Generally, patients with multisystem disease had a similar profile of radiological lesions as patients with isolated PLCH, except that the high severity of cystic lesions was significantly more common in MS-PLCH patients, compared with IPLCH patients [14 (40%) vs. 19 (20%); p = 0.023]. The involvement of supradiaphragmatic parts of both lungs was visualized (40 vs. 21%; p = 0.033) in a significant number of patients with MS-PLCH compared to IPLCH patients. In addition, higher intensity of small cysts in IPLCH compared to MS-PLCH patients [29 (31%) vs. 4 (11%); p = 0.025] was noticed. Relationships between radiological lesions and pulmonary function tests Functional tests were performed in patients with PLCH at the same time as the radiological images were obtained. Airway obstruction was found in 48 (38%) patients, and restriction was present in 7 (6%) patients. Pulmonary hyperinflation was detected in 73 (59%) patients. A reduced T LCO below 70% pred. was noted in 94 (74%) patients (Table 4 ). Table 4 Pulmonary function tests in PLCH patients. FVC% pred. (mean ± SD) N ALL N (%) IPLCH N (%) MS-PLCH P 127 87.8 ± 20.5 92 89.9 ± 20.3 35 82.2 ± 20.2 0.09 FEV1% pred. (mean ± SD) 127 65.7 ± 18.8 92 67.2 ± 20.1 35 61.6 ± 14.2 0.34 FEV1%/VC (mean ± SD) 127 75 ± 18.9 92 75.4 ± 19.0 35 74 ± 18.8 0.67 TCL% pred. (mean ± SD) 124 104 ± 17.5 90 104.8 ± 18.6 34 101.8 ± 14.0 0.39 RV% pred. (mean ± SD) 124 134.3 ± 45.7 90 132.6 ± 44.3 34 138.8 ± 49.6 0.72 TL CO % pred. (mean ± SD) 127 58.0 ± 16.7 92 58.5 ± 16.6 35 56.8 ± 17.4 0.47 FVC% < 70% pred. 23 (18%) 16 (17) 7 (20) 0.934 FEV1% < pred. 70% 60 (47%) 44 (48) 16 (48) 0.989 FEV1%/VC < 70% pred. 48 (38%) 35 (38) 13 (38) 0.911 TCL% 120% pred. 20 (16%) 15 (17) 5 (15) 0.968 RV% 120% pred. 73 (59%) 54 (60) 19 (56) 0.986 TL CO < 70% pred. 94 (74%) FEV 1 , forced expiratory volume in 1 s FVC, forced vital capacity HRCT, high-resolution computed tomography IPLCH, isolated pulmonary Langerhans cell histiocytosis MS-PLCH, multisystem Langerhans cell histiocytosis with lung involvement PLCH, pulmonary Langerhans cell histiocytosis pred., predicted RV, residual volume SD, standard deviation TLC, total lung capacity TL CO , diffusion lung capacity for carbon monoxide A negative correlation was found between the incidence of cysts and FEV1% pred. (R=-0.408; p = 0.0000), FEV1%/VC ratio (R=-0.343; p = 0.0001), and FVC% pred. (R=-0.262; p = 0.0029). In contrast, there was a positive relationship between the incidence of cysts and the RV% pred. (R = 0.378; p = 0.0000). There was no correlation between TLC% pred. and the intensity of the presence of cysts. Moreover, a negative correlation between the incidence of cysts and TL co (R=-0.540; p = 0.0000) was shown. There were no correlations between the intensity of nodules and pulmonary function tests. A significantly greater mean cystic score was found in patients with airway obstruction than in patients without airway obstruction (14.76 ± 6.30 vs. 10.04 ± 6.29; p = 0.0000), and the mean intensity of nodules in these patients was lower than that in patients without obstruction (3.54 ± 3.20 vs. 5.0 ± 3.46; p = 0.0198). In patients with signs of restriction, there was no correlation with the intensity of the cysts or nodules. There were no differences between patients with multisystem and isolated PLCH in terms of pulmonary function parameters. Table 4 . Multivariate analysis of the relationship between IPLCH and MS-PLCH groups In the multivariate analysis of the relationship between the IPLCH and MS-PLCH patient following factors were considered: gender, cigarette smoking, severity of nodular lesions, and severity of cystic lesions. It was found that cigarette smoking and the severity of cystic lesions, with a probability of 79.5%, classified patients as IPLCH, and with a probability of 20.5% to the MS-PLCH group. In contrast, patients categorized based on selected characteristics into the MS-PLCH group actually came from the IPLCH group with a probability of 11.1% (Table 5 ). Table 5 Analysis of the probability of belonging to the group of IPLCH or MS-PLCH Distortion table Assigned group Assigned group p = 0,0000 k = 4 IPLCH MS-PLCH Real group IPLCH 93 1 Real group MS-PLCH 24 8 Probability table Assigned group Assigned group IPLCH MS-PLCH Real group IPLCH 98,9% 1,1% Real group MS-PLCH 75% 25% Reliability table Real group Real group IPLCH MS-PLCH Assigned group IPLCH 79,5% 20,5% Assigned group MS-PLCH 11,1% 88,9% IPLCH, isolated pulmonary Langerhans cell histiocytosis MS-PLCH, multisystem Langerhans cell histiocytosis with lung involvement Table 5 . Analysis% pred.ents with a history of pneumothorax In PLCH patients, a negative correlation between age and the occurrence of pneumothorax (p < 0.00001) was shown. Moreover, men suffered from pneumothorax more often than women did (36% vs. 18%; p = 0.029), and patients with MS-PLCH were more likely to have pneumothorax than patients with IPLCH (51% vs. 46%; p = 0.0002). Patients with pneumothorax smoked fewer cigarettes than patients without this symptom (10.27 ± 8.59 vs. 21.04 ± 17.87 packs/year; p = 0.006). Among patients with pneumothorax, the presence of nodules (94% vs. 66%; p = 0.001) and cysts (94% vs. 87%; p = 0.006) was more common than in patients without pneumothorax. There was no correlation between the cystic score or the nodule score and the occurrence of pneumothorax. The group of patients with pneumothorax did not differ from the group without pneumothorax in terms of the presence of emphysema or cysts (Table 6 ). This means that people who developed pneumothorax were younger, smoked less tobacco, were male, and suffered from MS-PLCH more often. Table 6 Analysis of patients with pneumothorax in comparison with those without a history of this condition. Patients number All Patients without pneumothorax Patients with pneumothorax P 129 (100%) 95 (74%) 34 (26%) Age (years) (mean ± SD) 39.1 ± 14.1 40.69 ± 14.18 28.62 ± 9.99 0.00001 Women Men 68 (53%) 61 (47%) 56 (82%) 39 (64%) 12 (18%) 22 (36%) 0.029 IPLCH MS-PLCH 94 (73%) 35 (27%) 78 (54%) 17 (49%) 16 (46%) 18 (51%) 0.0002 Smoking (pack/years) (mean ± SD) 18.5 ± 16.8 21.04 ± 17.87 10.27 ± 8.59 0.006 Marijuana smoking 17 (13%) 10 (11%) 7 (24%) 0.148 Cysts score (mean ± SD) 11.9 ± 6.7 11.56 ± 6.87 13.0 ± 6.09 0.237 Nodules score (mean ± SD) 4.4 ± 3.4 4.75 ± 3.59 3.56 ± 2.78 0.119 Cysts 115 (89%) 83 (87%) 32 (94%) 0.006 Small intensity of cysts 33 (26%) 27 (28%) 6 (18%) 0.314 Medium intensity of cysts 38 (29%) 28 (29%) 10 (29%) 0.837 High intensity of cysts 33 (26%) 23 (24%) 10 (29%) 0.862 Very high intensity of cysts 25 (19%) 17 (18%) 8 (24%) 0.859 Emphysema 40 (31%) 30 (32%) 10 (29%) 0.816 Number of patients with nodules 95 (73%) 63 (66%) 32 (94%) 0.001 IPLCH, isolated pulmonary Langerhans cell histiocytosis MS-PLCH, multisystem Langerhans cell histiocytosis with lung involvement Table 6 . Discussion In patients with PLCH, chest CT findings play a key role not only in guiding the diagnosis but also, in many cases, it is a basis for it. The disease is on a spectrum of smoking-related diseases, and despite lesions characteristic of PLCH, lesions characteristic of other diseases can be present. In this study, we evaluated these disease-specific radiological lesions in a large group of PLCH patients. No variations in sex, age, smoking habits, or other demographic parameters were observed in our patients in comparison to previously presented patients [ 3 , 5 , 7 – 12 ]. Owing to the often asymptomatic course of the disease (approximately 30%), nonspecific and poorly expressed symptoms, which are downplayed, especially by young people, a relatively significant diagnostic delay is observed. In addition, the fact that the chest radiograph, sometimes assessed as normal, often affects the prolongation of diagnosis. This situation was present in both the studied group, the European [ 3 ] and Chinese [ 22 ] populations, and was 18.8, 24, and 17 months long, respectively. Pneumothorax is a characteristic symptom of cystic lung diseases and is the first symptom in 11.7–25% of PLCH patients [ 1 – 3 , 5 , 18 , 22 ]. Moreover, pneumothorax is more common in younger patients, those who smoke less, men, and those with multisystem disease [ 23 , 24 ]. Similar observations regarding radiological findings were published by Kim et al. [ 10 ] in a group of 27 PLCH patients. In these studies, nodules and cysts were the most common radiological lesions observed in 89% and 82% of patients, respectively, whereas reticular lesions were present in 19% of patients. Elia et al., in a group of 40 PLCH patients, visualized cysts in 63% of patients, whereas nodules were observed in only 23% of patients [ 25 ]. In a study by Miao et al., cysts and nodules were observed in 51% and 46% of 109 patients with PLCH, respectively [ 22 ]. In 112 patients with PLCH reported by Hazim et al., cysts and nodules were observed in 67% and 33% of patients, respectively [ 26 ]. Benattia et al., in a group of 196 patients, presented that 90% of them exhibited a nodulo-cystic pattern of lesions [ 8 ]. The occurrence of emphysema and reticular and honeycomb lesions in PLCH patients was analysed by Koyama et al. [ 11 ]. These authors reported emphysema in 5 of 18 patients, reticular lesions, and honeycomb lesions in two and one patient, respectively. Ground glass opacities were visualized in 58% of Japanese patients and in 3 out of 14 patients by Vassallo et al. [ 11 , 12 ]. Bronchiectasis in those studies was observed in 6% and 8% of patients. A detailed evaluation of the nature of the cystic lesions in the present study revealed that thin-walled cysts were the most common (89% of patients). Thick-walled cysts were detected in 43% of the patients, and sinusoidal cysts were detected in 60% of the patients. There are isolated publications in the available literature that evaluate in detail the nature of cysts in PLCH. Kim et al. visualized thin-walled cysts in 82% of 27 patients, thick-walled cysts in 82%, and sinusoidal cysts less frequently in only 41% of patients [ 10 ]. In contrast, Rodrigues et al., in a group of 8 patients, imaged thick-walled cysts in half of the patients [ 26 ]. In the present group of patients, nodules 10 mm in diameter were detected in 24% and 2% of patients, respectively. Quantitative evaluation of the morphological changes among the studied patients revealed that the mean intensity of the nodules was lower than that of the cysts (4.4 ± 3.4 vs. 11.9 ± 6.7). These results were similar to those reported by Tazi et al., who reported that, in a group of 49 patients, the mean intensities of nodular and cystic lesions were 6.6 ± 3.4 and 11.9 ± 6.1, respectively [ 18 ], but in a recent data from this group mean nodular score was 6.8, and mean cystic score was also 6.8 [ 8 ]. In a group of 196 patients, Benattia et al. reported that HRCT cystic scores were predominantly low to intermediate in 175 patients (89.3%), potentially indicating an earlier stage of the disease [ 8 ]. In our patient cohort, this scoring pattern was observed in 55% of individuals, indicating that our patients had more advanced stages of the disease. This phenomenon can be attributed to disease progression, where initial nodular lesions are more prevalent, followed by the development of cavitary nodules and, eventually, the emergence of thick- and thin-walled cysts. The extended period before diagnosis contributes to patients presenting with more advanced disease [ 7 – 10 ]. Recently, Poellinger et al. described a specific new “octopus sign” in the radiological presentation of PLCH patients. It corresponds to small septal fibrotic strands emanating from a central bronchiolocentric scar that form a typical appearance resembling a star. It is suggested that the octopus sign could be helpful to differentiate between certain stages of LCH and centrilobular emphysema [ 28 ]. Our study was performed earlier, and this sign was not assessed. Numerous publications emphasize the fact that the disease spares the supradiaphragmatic parts of the lungs. In a publication by Elia et al., the lower parts of the lungs were spared in 62% of patients [ 25 ]. Vassallo et al. reported a predominance of lesions in the upper and middle portions of the lungs in 18 of 29 patients [ 12 ]. In contrast, Kim et al. reported lower lung lesions in only 3 of 27 patients [ 10 ]. However, these analyses were quite general. In our study, in 50% of the patients, both the anterior and posterior parts of the lung base, i.e., the free basal parts of the middle lobe and lingula, were free from lesions, as were the free basal parts of the lower lobes. In addition, quite often, only the anterior parts were free of lesions (19%). Lesion-free only basal parts of the lower lobes of the lungs were observed in a small percentage (5%) of patients. The involvement of all supradiaphragmatic portions of the lungs was visualized in 26% of the PLCH patients. This detailed analysis is presented for the first time. Hilar and mediastinal lymphadenopathy is not a highly characteristic feature among adult PLCH patients and has been demonstrated in 6–20% of presented patients [ 1 – 3 , 22 ]. Mean values of pulmonary function tests observed in our group were like to those previously published [ 8 , 18 , 26 – 27 , 29 – 31 ]. In addition, there was a negative correlation between the incidence of cysts and FEV1% pred. (p = 0.0000), FEV1%/VC ratio (p = 0.0001), FVC% pred. (p = 0.0029), and TL co % pred. (p = 0.0000), and a positive correlation between RV% pred. (p = 0.0000). The relationship between radiological images and functional tests has also been presented by other authors. Canuet et al. reported an association between the incidence of cysts and the FEV1/VC ratio (p = 0.01) and TL co (p < 0.01) in 26 PLCH patients [ 31 ]. Tazi et al., in a retrospective analysis of 49 patients, did not detect a significant correlation between the intensity of nodules incidence and lung ventilation parameters. In contrast, the degree of cyst presence was strongly correlated with a decrease in the FEV1%, FEV1%/VC ratio (p < 0.0001) and TL co % pred. (p = 0.01) [ 18 ]. These observations support the fact that patients with a predominant pattern of nodular changes on CT scans are in the early stages of PLCH, with few consequences for their respiratory parameters. The focus of this study was the evaluation of findings visualized by HRCT in PLCH patients and to analyse differences in radiological presentation between patients with isolated and multisystem PLCH. We presented that IPLCH patients did not differ from MS-PLCH patients in the degree of functional lung damage, impaired carbon monoxide transfer factor. The above observations are unique and have not been reported in the literature. Another issue not previously analysed in the literature was an attempt to answer the question of whether there are radiological and/or clinical factors to differentiate the group of patients with IPLCH from those with MS-PLCH. The fact of higher smoking intensity and lower severity of cystic lesions was associated with a higher probability of isolated lung involvement. It was determined that patients with a probability of 79.5% classified as IPLCH actually came from this group, and with a probability of 20.5% from the MS-PLCH group. In contrast, patients classified on the basis of selected characteristics into the MS-PLCH group were actually from the IPLCH group with a probability of 11.1%. The algorithm used in this analysis for the IPLCH and MS-PLCH patient groups could be applied to the work of radiologists and clinicians, helping predict the extent of the disease. A limitation of the study is that it was a retrospective, single-center study. However, this was one of the largest analysed populations of histologically confirmed PLCH patients, and the study was performed at the Expert Center for Rare Diseases, which belongs to the ERN-LUNG. Abbreviations COPD, chronic obstructive pulmonary disease GERD, gastroesophageal reflux disease FEV 1 , forced expiratory volume in 1 s FVC, forced vital capacity HRCT, high-resolution computed tomography IPLCH , isolated pulmonary Langerhans cell histiocytosis MRI, MS-PLCH , multisystem Langerhans cell histiocytosis with lung involvement PaO 2 , partial pressure of oxygen in the blood PaCo2, partial pressure of carbon dioxide in the blood PLCH , pulmonary Langerhans cell histiocytosis pred., predicted RV, residual volume SD, standard deviation TLC, total lung capacity TL CO , diffusion lung capacity for carbon monoxide Declarations Ethics approval and consent to participate The study was approved by the National Tuberculosis and Lung Diseases Ethics Committee (No. KB-11/2019). All patients provided written informed consent for the use of their medical records for research. Consent for publication The other editorial board does not consider the article. All authors approved this manuscript and declared no conflict of interest. Availability of data and materials All source data are available on request Competing interests All authors declared no conflict of interest. Funding The study was approved by the Internal Review Board of the National Tuberculosis and Lung Disease Institute and was supported by the grant No. 7.33/2018. Authors' contributions Study conception and design: ER, MJ, IB. Acquisition of data: ER, MS, JM-D, RL, SW, WN, DJ, WK. Assessment of radiological findings: MJ, KB, IB, KO, BB, JW. Analysis of data, drafting, and writing of the manuscript [ER, MJ, IB]. All authors contributed to reviewing the manuscript and approved the final version for publication References Goyal G, Tazi A, Go RS, et al. International expert consensus recommendations for the diagnosis and treatment of Langerhans cell histiocytosis in adults. Blood. 2022;139:2601–21. Girschikofsky M, Arico M, Castillo D, et al. Management of adult patients with Langerhans cell histiocytosis: recommendations from an expert panel on behalf of Euro-Histio-Net. Orphanet J Rare Dis. 2013;8:72. Aricò M, Girschikofsky M, Généreau T, et al. Langerhans cell histiocytosis in adults. Report from the International Registry of the Histiocyte Society. Eur J Cancer. 2003;39:2341–8. Elia D, Torre O, Cassandro R, et al. Pulmonary Langerhans cell histiocytosis: a comprehensive analysis of 40 patients and literature review. Eur J Int Med. 2015;26:351–6. Goyal G, Hu M, Young JR, et al. Adult Langerhans cell histiocytosis: A contemporary single-institution series of 186 patients. J Clin Oncol. 2019;37:7018. Liu H, Stiller CA, Crooks CJ, Rous B, Bythell M, Broggio J, Rankin J, Nanduri V, Lanyon P, Card TR, Ban L, Elliss-Brookes L, Broughan JM, Paley L, Wong K, Bacon A, Bishton M, West J. Incidence, prevalence and survival in patients with Langerhans cell histiocytosis: A national registry study from England, 2013–2019. Br J Haematol. 2022;199(5):728–38. 10.1111/bjh.18459 . Epub 2022 Sep 19. PMID: 36122574; PMCID: PMC9826274. Tazi A, de Margerie C, Naccache JM, et al. The natural history of adult pulmonary Langerhans cell histiocytosis: a prospective multicentre study. Orphanet J Rare Dis. 2015;10:30. Benattia A, Bugnet E, Walter-Petrich A, et al. Long-term outcomes of. Adult pulmonary Langerhans cell histiocytosis: a prospective cohort. Eur Resp J. 2022;59:2101017. doi.org/10.1183/13993003.01017-2021 . Radzikowska E. Update on Pulmonary Langerhans Cell Histiocytosis. Front Med (Lausanne). 2021;7:582581. Kim HJ, Lee KS, Johkoh T, et al. Pulmonary Langerhans cell histiocytosis in adults: high-resolution CT-pathology comparisons and evolutional changes at CT. Eur Radiol. 2011;21:1406–15. Koyama M, Johkoh T, Honda O, et al. Chronic cystic lung disease: Diagnostic accuracy of high-resolution CT in 92 patients. Am J Roentgenol. 2003;180:827–35. Vassallo R, Ryu JH, Schroeder DR, et al. Clinical outcomes of pulmonary Langerhans'-cell histiocytosis in adults. N Eng J Med. 2002;346:484–90. Vassallo R, Jensen E, Colby T, et al. The overlap between respiratory bronchiolitis and desquamative interstitial pneumonia in pulmonary Langerhans cell histiocytosis: high-resolution CT, histologic, and functional correlation. Chest. 2003;124:1199–205. 10.1378/chest.124.4.1199 . Le Pavec J, Lorillon G, Jaïs X, et al. Pulmonary Langerhans cell histiocytosis-associated pulmonary hypertension: clinical characteristics and impact of pulmonary arterial hypertension therapies. Chest. 2012;142:1150–7. Bois M, May A, Vassallo R, et al. Morphometric study of pulmonary arterial changes in pulmonary Langerhans cell histiocytosis. Arch Pathol Lab Med. 2018;142:929–37. Heiden GI, Sobral JB, Freitas CSG, et al. Mechanisms of exercise limitation and prevalence of pulmonary hypertension in pulmonary Langerhans cell histiocytosis. Chest. 2020;158:2440–8. Bankier AA, MacMahon H, Colby T, et al. Fleischner Society: Glossary of terms for thoracic imaging. Radiology. 2024;310:232558. https://doi.org/10.1148/radiol.23255 . Tazi A, Marc K, Dominique S, et al. Serial computed tomography and lung function testing in pulmonary Langerhans' cell histiocytosis. Eur Respir J. 2012;40:905–12. Graham BL, Steenbruggen I, Miller MR, et al. Standardization of Spirometry 2019 Update an official American Thoracic Society and European Respiratory Society Technical Statement. Am J Respir Crit Care Med. 2019;200:8, e70–88. Graham BL, Brusasco V, Burgos F, et al. ERS/ATS standards for single-breath carbon monoxide uptake in the lung. Eur Respir J. 2017;49:1600016. Holland AE, Spruit MA, Troosters T, et al. An official European Respiratory Society/American Thoracic Society technical standard: field walking tests in chronic respiratory disease. Eur Respir J. 2014;44:1428–46. Miao H, Zhao A, Duan M, et al. Clinical presentation and prognostic analysis of adult patients with Langerhans cell histiocytosis with pulmonary involvement. BMC Cancer. 2020;20:911. Radzikowska E, Błasińska-Przerwa K, Wiatr E, et al. Pneumothorax in Patients with Pulmonary Langerhans Cell Histiocytosis. Lung. 2018;196:715–20. Mendez JL, Nadrous HF, Vassallo R, Decker PA, Ryu JH. Pneumothorax in pulmonary Langerhans cell histiocytosis. Chest. 2004;125:1028–32. Elia D, Torre O, Cassandro R, Caminati A, Harari S. Pulmonary Langerhans cell histiocytosis: a comprehensive analysis of 40 patients and literature review. Eur J Intern Med. 2015;26(5):351–6. 10.1016/j.ejim.2015.04.001 . Epub 2015 Apr 17. PMID: 25899682. Hazim AZ, Ruan GJ, Hu M, et al. Langerhans cell histiocytosis with lung involvement in isolation and multisystem disease: Staging, natural history, and comparative survival. Am J Hematol. 2021;96:1604–10. Rodrigues RS, Capone D, Ferreira Neto AL, et al. High-resolution computed tomography findings in pulmonary Langerhans cell histiocytosis. Radiol Bras. 2011;44:225–32. Poellinger A, Berezowska S, Myers JL, et al. The Octopus Sign-A New HRCT Sign in Pulmonary Langerhans Cell Histiocytosis. Diagnostics (Basel). 2022;12:937. 10.3390/diagnostics12040937 . Schönfeld N, Dirks K, Costabel U, Loddenkemper R.. A prospective clinical multicentre study on adult pulmonary Langerhans’ cell histiocytosis. Sarcoidosis Vasc Diff Lung Dis. 2012;29:132–8. Li C, Li M, Li J, et al. Pulmonary Langerhans cell histiocytosis: analysis of 14 patients and literature review. J Thorac Dis. 2016;8:1283–9. Canuet M, Kessler R, Jeung MY, et al. Correlation between high-resolution computed tomography findings and lung function in pulmonary Langerhans cell histiocytosis. Respiration. 2007;74:640–6. Additional Declarations No competing interests reported. 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13:08:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9357366/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9357366/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":109340909,"identity":"b00b9e28-a60b-4879-b029-89e8accd3f7e","added_by":"auto","created_at":"2026-05-15 18:50:27","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":528107,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9357366/v1/39431ffb-54ff-4287-86ed-b7ca30961689.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eLung structure disorders visualized by chest computed tomography in patients with pulmonary Langerhans cell histiocytosis and their correlation with the pulmonary function tests and disease extension\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePulmonary Langerhans cell histiocytosis (PLCH) is a rare disease characterized by the proliferation of Langerhans cells burdened with mutations in mitogen-stimulated kinase pathway genes accompanied by inflammation, which causes progressive destruction of the surrounding tissues [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The lungs may be involved as an isolated organ (IPLCH) or as one of many organs involved in a multisystem disease (MS-PLCH). The disease occurs predominantly in young adults, without sex predominance. Incidence rate of LCH is about 1/ million adults, with prevalence about 10/million [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Approximately 90\u0026ndash;95% of PLCH patients are tobacco smokers, and 10\u0026ndash;20% are marijuana smokers [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan additionalcitationids=\"CR6 CR7 CR8\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Radiological examinations are among the most important elements leading to diagnosis. Particularly noteworthy is high-resolution computed tomography (HRCT), which is often considered to be specific. The typical findings are centrilobular nodules (with a \u0026ldquo;tree-in-bud\u0026rdquo; appearance), cavitated nodules, and initially thick-walled cysts of various shapes. As the disease progresses, the cysts become larger and thin-walled with bizarre shapes. Lesions have a characteristic distribution with a predominance in the upper and middle parts of the lungs [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan additionalcitationids=\"CR6 CR7 CR8 CR9 CR10\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. In PLCH patients, other radiological symptoms of smoking-related diseases are often visible (e.g., emphysematous bullae or ground glass opacities) [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Enlarged lymph nodes may be present in approximately 10% of affected patients. Signs of pulmonary hypertension and heart and pulmonary trunk enlargement are observed in patients with advanced disease [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eThe aim of this study was to investigate the correlation of disturbances in lung architecture visualized by chest CT with pulmonary function tests in patients with PLCH. Special attention was paid on differences in radiological picture between patients with isolated PLCH and those with multisystem disease with lung involvement.\u003c/p\u003e"},{"header":"Materials","content":"\u003cp\u003eThe study included a retrospective evaluation of PLCH patients hospitalized at the Institute of Tuberculosis and Lung Diseases in Warsaw from 2007\u0026ndash;2021 at the time of first presentation.\u003c/p\u003e\n\u003cp\u003eDuring this period, the diagnosis of PLCH was established in 147 patients; however, owing to insufficient radiological documentation, 129 patients were analysed.\u003c/p\u003e\n\u003cp\u003ePatients met the following criteria: the clinical and radiological findings were consistent with LCH, other diseases that could be the cause of the observed changes were excluded, and/or the diagnosis was confirmed by histological examination.\u003c/p\u003e\n\u003cp\u003eClinical data concerning age, sex, tobacco and marijuana smoking status, concomitant diseases, diagnostic delay, symptoms of the disease at the time of diagnosis, especially the presence of pneumothorax, the extent of the disease, and pulmonary function tests. Thoracic CT was assessed by experienced pulmonary radiologists (MJ, IB, KB, KO, BB).\u003c/p\u003e\n\u003cp\u003eTo determine the extent of the disease, laboratory tests, craniofacial CT, MRI of the brain and pituitary gland, PET/CT, bone scintigram, and ultrasound of the heart, abdominal cavity, and thyroid gland were performed, and changes in the bones or spinal cord were additionally confirmed by CT or magnetic resonance imaging tests dedicated to their assessment.\u003c/p\u003e\n\u003cp\u003eThe extent of the disease was determined according to the criteria proposed by the Histiocytosis Society [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Internal Review Board of the National Tuberculosis and Lung Disease Institute No. 7.33/2018.\u003c/p\u003e\n\u003cp\u003eThe Ethics Committee of the National Tuberculosis and Lung Disease Institute approved this study (No. KB-11/2019). All patients provided written informed consent for the use of their medical records for research.\u003c/p\u003e\n\u003cp\u003eMethods\u003c/p\u003e\n\u003cp\u003ePulmonary window CT (window parameters: W-1500; L-700) was used to qualitatively evaluate the presence of PLCH lesions, including nodules with disintegration, cysts, foci of shadowing with a ground-glass appearance, reticular lesions, emphysema, bronchial dilatation, and honeycomb lesions.\u003c/p\u003e\n\u003cp\u003eQualitative morphological evaluation of the lesions was performed in accordance with the Fleischner Society definitions [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eThe chest CT analysis utilized the assessment method outlined by Tazi et al. [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Each lung was divided into three fields: upper, middle, and lower. The upper field included the lung from the peak to the level of the tracheal bifurcation, the middle field from the tracheal bifurcation to the inferior pulmonary venous drainage, and the lower field below the level of the inferior pulmonary venous drainage to the level of the diaphragm. In addition, the supradiaphragmatic parts of the lungs were specified, dividing them into an anterior part, including the basal parts of the middle lobe and lingual lobe, and a posterior part, including the supradiaphragmatic parts of the basal segments of the lower lobes.\u003c/p\u003e\n\u003cp\u003eNodules were divided by size into nodules\u0026thinsp;\u0026lt;\u0026thinsp;5 mm in diameter, nodules between 5\u0026ndash;10 mm, and nodules\u0026thinsp;\u0026gt;\u0026thinsp;10 mm. Nodules were quantitatively assessed on a four-point scale, depending on their percentage in each of the six lung fields (0\u0026ndash;free lung field; 1\u0026ndash;occupied\u0026thinsp;\u0026lt;\u0026thinsp;25%; 2\u0026ndash;between 25\u0026ndash;50%; 3\u0026ndash;occupied\u0026thinsp;\u0026gt;\u0026thinsp;50%). The points from each lung field were then summed. The intensity of the nodules was determined as follows: low (0\u0026ndash;6 points), medium (7\u0026ndash;12 points), or high (13\u0026ndash;18 points).\u003c/p\u003e\n\u003cp\u003eThe cysts were divided according to wall thickness into thin-walled cysts (\u0026lt;\u0026thinsp;2 mm) and thick-walled cysts (\u0026gt;\u0026thinsp;2 mm). The above-described cystic lesions were quantitatively assessed on the four-grade scale described below according to their percentage in each of the six lung fields mentioned above (0- free lung field; 1- occupied\u0026thinsp;\u0026lt;\u0026thinsp;25%; 2- occupied between 25\u0026ndash;50%; 3- occupied between 50\u0026ndash;75%; 4\u0026ndash; occupied\u0026thinsp;\u0026gt;\u0026thinsp;75%). The estimated points from each lung field were then summed. On this basis, the intensity of the cysts was classified as follows: low, 0\u0026ndash;6 points; medium, 7\u0026ndash;12 points; high, 13\u0026ndash;18 points; and very high, 19\u0026ndash;24 points.\u003c/p\u003e\n\u003cp\u003eA CT cross-section of the chest containing the most severe lesions was selected for quantitative evaluation of each lung field.\u003c/p\u003e\n\u003cp\u003eOwing to the characteristics of the disease, special attention was given to assessing the supradiaphragmatic parts of the lungs according to the following criteria: 1- supradiaphragmatic portions of the lungs; 2- free anterior supradiaphragmatic parts\u0026mdash;free basal parts of the middle lobe and lingula; 3- free posterior supradiaphragmatic parts\u0026mdash;free basal parts of the lower lobes; and 4- free anterior and posterior supradiaphragmatic parts\u0026mdash;free basal parts of both the middle lobe and lingula as well as the lower lobes.\u003c/p\u003e\n\u003cp\u003ePulmonary function tests were performed according to the joint guidelines of the American Thoracic Society and the European Respiratory Society. The lung volume was measured via body plethysmography (MasterScreen software, ver. 4.65; Jeager, Wuerzburg, Germany), and the transfer factor of the lung for carbon monoxide (T\u003csub\u003eLCO\u003c/sub\u003e) was determined via the single-breath technique [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. The 6-min walk test (6MWT) was performed as recommended by the ATS [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical methods\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003eStatistical analyses were performed via the STATISTICA statistical package (data analysis software system), version 9.0, by StatSoft, Inc. (2009) (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ewww.statsoft.com\u003c/span\u003e\u003c/span\u003e). Only nonparametric tests were used because the data did not meet the condition of normality of distributions. For the analysis of relationships between qualitative variables, contingency tables, and the chi-square test or one of its modifications, the chi-square test or the Yates test was used. The relationships between two quantitative variables were analysed via Spearman\u0026apos;s rank correlation test. The relationships between the quantitative and qualitative variables were tested with the Mann‒Whitney test.\u003c/p\u003e\n\u003cp\u003eThe multivariate analysis used a combination of two methods from the field of pattern recognition, the k nearest neighbour rule (k-NS), the minus one element method and the chi-square test. The k-NS rule makes it possible to identify a group of patients based on knowledge of either the values of all features or a selected combination of them.\u003c/p\u003e\n\u003cp\u003eAll \u003cem\u003eP\u003c/em\u003e values are two-sided and were considered to reflect a statistical significance of \u0026lt;\u0026thinsp;0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy group\u003c/h2\u003e \u003cp\u003eA group of 129 patients (55% women) with PLCH was evaluated (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The mean age of the patients at diagnosis was 39.1 (\u0026plusmn;\u0026thinsp;14.1) years. Isolated PLCH (IPLCH) was diagnosed in 94 patients, and 35 patients had multisystem LCH with lung involvement (MS-PLCH). Nearly all patients were cigarette smokers (96%). Passive exposure to tobacco smoke was noted in 3 (2.5%) patients, and 2 (1.5%) patients had never smoked. The mean intensity of smoking was 18.5\u0026thinsp;\u0026plusmn;\u0026thinsp;16.8 packs/year. Seventeen (13%) patients smoked marijuana. There were no differences between IPLCH and MS-PLCH according to age and gender; however, a significantly higher number of nonsmokers were noticed in MS-PLCH group than in IPLCH (1 vs.11%; p\u0026thinsp;=\u0026thinsp;0.022). In addition, patients with MS-PLCH smoked fewer cigarettes than patients with IPLCH (12.3\u0026thinsp;\u0026plusmn;\u0026thinsp;11.9 vs. 20.07\u0026thinsp;\u0026plusmn;\u0026thinsp;17.7 pack/years; 0.007).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of PLCH patients.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePatients number\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll\u003c/p\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIPLCH\u003c/p\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMS-PLCH N (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e129\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e94(73)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35(27)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.330\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWomen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68 (53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52(55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16(46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61 (47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42(45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19(54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmokers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e124 (96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e93(99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31(89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.987\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-smokers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e1(1)\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e4(11)\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e0.022\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMarijuana users\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (13%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13(14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4(11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.947\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking pack/years (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18.5\u0026thinsp;\u0026plusmn;\u0026thinsp;16,8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.07\u0026thinsp;\u0026plusmn;\u0026thinsp;17.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.3\u0026thinsp;\u0026plusmn;\u0026thinsp;11.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39.1\u0026thinsp;\u0026plusmn;\u0026thinsp;14,1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40\u0026thinsp;\u0026plusmn;\u0026thinsp;14.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36.14.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence of CD1a and/or CD207\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e90 (70%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61(65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29(83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStellar scars\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (13%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14(15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.34\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBAL\u0026thinsp;\u0026gt;\u0026thinsp;5% CD1a positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiagnosis based on clinical and radiological picture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (15%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16(17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMS-PLCH\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35 (27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePituitary gland\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (12.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16 (46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFacial bones\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (11.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCranial bones\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBrain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (3.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSkin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGingiva\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLiver\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0ther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eBAL, bronchoalveolar lavage\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eIPLCH, isolated pulmonary Langerhans cell histiocytosis\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eMS-PLCH, multisystem Langerhans cell histiocytosis with lung involvement\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003ePLCH, pulmonary Langerhans cell histiocytosis\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eSD- standard deviation\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eA definite diagnosis based on the characteristic microscopy image and the expression of the CD1a and/or CD207 antigen was established in 90 (70%) patients. In 17 (13%) patients, histological examination revealed the evolution of histiocytic lesions with the formation of stellar-shaped scars. The presence of \u0026gt;\u0026thinsp;5% CD1a-positive cells in the bronchoalveolar lavage fluid was detected in 3 (2%) patients. Characteristic clinical and radiological findings and the exclusion of other causes of the disease were the basis of diagnosis in 19 (15%) patients. More frequently, CD1a and CD207 positive cells were detected in patients with MS-PLCH than in IPLCH ( 83 vs. 65%; p\u0026thinsp;=\u0026thinsp;0.004).\u003c/p\u003e \u003cp\u003eAmong the 35 patients with MS-PLCH the most commonly involved organs were the pituitary gland, facial bones, skull bones, skin, brain, liver, mucous membranes and other bones (spine, ribs, femurs and hip bone) in: 16 (46%), 15 (43%), 13 (37%), 4(11%), 5(14%), 2(6%), 3 (9%) and in 4 (11%) patients respectively. MS-PLCH with involvement of high-risk organs was diagnosed in seven (20%) patients.\u003c/p\u003e \u003cp\u003eThe frequencies of symptoms and concomitant diseases are shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eConcomitant diseases and symptoms in PLCH patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConcomitant diseases\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll\u003c/p\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIPLCH\u003c/p\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMS-PLCH\u003c/p\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGERD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35 (27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.428\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCOPD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.967\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eObesity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.180\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArterial hypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.289\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThyroid diseases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.133\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAsthma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.964\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.446\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAutoimmune diseases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.055\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoronary artery disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.727\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCholecystolithiasis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.874\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypoxemic respiratory failure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.628\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRespiratory failure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDepression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMyoma uteri\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.208\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlcohol abuse\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.464\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClinical symptoms\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCough\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e92 (71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67 (71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25 (71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.839\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDecreased exercise tolerance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e83 (64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59 (62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24 (69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.685\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDyspnoea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e75 (58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55 (59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 (57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.516\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSputum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23\u0026nbsp;(24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.976\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLoss of weight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38 (29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8\u0026nbsp;(23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.431\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSweats\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.599\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.673\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBone pain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePneumothorax\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35(27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17(18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18 (51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eCOPD, chronic obstructive pulmonary disease\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eGERD, gastroesophageal reflux disease\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePatients with multisystem disease had similar pulmonary symptoms to those with isolated PLCH, but more frequently experienced bone pains (23 vs 2%; p\u0026thinsp;=\u0026thinsp;0.0004) and pneumothorax ( 51 vs 18%; p\u0026thinsp;=\u0026thinsp;0.0002) than IPLCH patients.\u003c/p\u003e \u003cp\u003ePatients with IPLCH had a similar profile of comorbidities as patients with MS-PLCH.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eAnalysis of radiological lesions\u003c/h3\u003e\n\u003cp\u003eThe lesions found on HRCT were cysts in 115 (89%), nodules in 95 (73%), emphysema in 40 (31%) patients, reticular lesions in 28 (22%) patients, cavitary nodules in 27 (21%) patients, and ground glass opacities in 14 (11%) patients. Bronchial dilatation and honeycomb-like lesions were relatively rarely observed, in 9 (7%) patients and 1(1%) patient, respectively (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of lesions detected by computed tomography in PLCH patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePatients number\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll\u003c/p\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIPLCH\u003c/p\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMS-PLCH\u003c/p\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e129\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e94(73)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35(27)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNodules\u0026thinsp;\u0026lt;\u0026thinsp;5 mm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e95 (73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e71(75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24(68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.425\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNodules 5 do 10 mm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24(26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7(20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.513\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNodules\u0026thinsp;\u0026gt;\u0026thinsp;10 mm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.807\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCavitated nodules\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21(22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6(17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.519\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThin-walled cysts\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e115 (89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e84(89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31(89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThick-walled cysts\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55 (43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39(41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16(46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.666\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLacunar cysts\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e78 (60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54(57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24(69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.197\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEmphysema\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40 (31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28(30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12(35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.623\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReticular lesions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20(21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8(23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.847\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGround glass opacities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.898\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBronchiectasis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.262\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHoneycombing changes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHilar and mediastinal lymphadenopathy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.664\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMediastinal lymphadenopathy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.992\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHilar lymphadenopathy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.612\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulmonary artery truncus\u0026thinsp;\u0026gt;\u0026thinsp;30 mm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8(9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.991\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean intensity of nodules\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4,4\u0026thinsp;\u0026plusmn;\u0026thinsp;3,4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.257\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntensity of nodules\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e95 (74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67 (71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28 (80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.317\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.513\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean intensity of cysts\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11,9\u0026thinsp;\u0026plusmn;\u0026thinsp;6,7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.3\u0026thinsp;\u0026plusmn;\u0026thinsp;6.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.4\u0026thinsp;\u0026plusmn;\u0026thinsp;6.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.098\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntensity of cysts\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33 (26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.025\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38 (29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.893\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33 (26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 (40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.023\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVery high\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.931\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAssessment of supradiaphragmatic parts\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLesions in supradiaphragmatic parts\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 (26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 (40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.033\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWithout lesions in basal parts of meddle lobe and lingula\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.203\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWithout lesions in basal parts of lower lobes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.727\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWithout lesions in basal parts of meddle lobe, lingula and lower lobes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49 (52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.349\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eIPLCH, isolated pulmonary Langerhans cell histiocytosis\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eMS-PLCH, multisystem Langerhans cell histiocytosis with lung involvement\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003c/p\u003e \u003cp\u003eNodules\u0026thinsp;\u0026lt;\u0026thinsp;5 mm in diameter were the most common and were observed in 95 (74%) patients. Nodules between 5\u0026ndash;10 mm in diameter and nodules\u0026thinsp;\u0026gt;\u0026thinsp;10 mm in diameter were detected in 31 (24%) and 3 (2%) patients, respectively.\u003c/p\u003e \u003cp\u003eThin-walled cysts were the most common morphological lesions and were visualized in 115 (89%) patients. Thick-walled cysts and sinusoidal cysts were detected in 55 (43%) and 78 (60%) patients, respectively.\u003c/p\u003e \u003cp\u003eThe mean intensity of the nodules was 4.4 (\u0026plusmn;\u0026thinsp;3.4). In 95 (74%) patients, the intensity of the nodules was low, medium in 31 (24%) patients, and high in 3 (2%) patients.\u003c/p\u003e \u003cp\u003eThe intensity of the cysts was as follows: small, medium, high, and very high in 33 (26%), 38 (29%), 33 (26%), and 25 (19%) patients, respectively. The mean score of the cysts was 11.9 (\u0026plusmn;\u0026thinsp;6.7). A negative correlation was found between the intensity of the cysts and the intensity of the nodules (R=-0.319; p\u0026thinsp;=\u0026thinsp;0.0002).\u003c/p\u003e \u003cp\u003eWidening of the pulmonary artery trunk\u0026thinsp;\u0026gt;\u0026thinsp;30 mm was demonstrated in 11 (9%) patients. Hilar and mediastinal lymphadenopathy was detected in 21 (16%) patients. The hilar lymph nodes were enlarged in 12 (9%) patients, whereas the mediastinal lymph nodes were enlarged in 9 (7%) patients.\u003c/p\u003e \u003cp\u003eThe most common lesion-free parts of the supradiaphragmatic lungs were both anterior and posterior, that is, the basal parts of the middle lobe and uvula and the basal parts of the lower lobes at the same time. This pattern of distribution was observed in 64 (50%) patients. In addition, quite often, only the anterior parts were free of lesions in 24 (19%) patients, and only the posterior portions of the lung base were free in only 7 (5%) patients. In 34 (26%) patients, the supradiaphragmatic parts of the lungs were involved in the disease process.\u003c/p\u003e \u003cp\u003eGenerally, patients with multisystem disease had a similar profile of radiological lesions as patients with isolated PLCH, except that the high severity of cystic lesions was significantly more common in MS-PLCH patients, compared with IPLCH patients [14 (40%) vs. 19 (20%); p\u0026thinsp;=\u0026thinsp;0.023]. The involvement of supradiaphragmatic parts of both lungs was visualized (40 vs. 21%; p\u0026thinsp;=\u0026thinsp;0.033) in a significant number of patients with MS-PLCH compared to IPLCH patients. In addition, higher intensity of small cysts in IPLCH compared to MS-PLCH patients [29 (31%) vs. 4 (11%); p\u0026thinsp;=\u0026thinsp;0.025] was noticed.\u003c/p\u003e\n\u003ch3\u003eRelationships between radiological lesions and pulmonary function tests\u003c/h3\u003e\n\u003cp\u003eFunctional tests were performed in patients with PLCH at the same time as the radiological images were obtained.\u003c/p\u003e \u003cp\u003eAirway obstruction was found in 48 (38%) patients, and restriction was present in 7 (6%) patients. Pulmonary hyperinflation was detected in 73 (59%) patients. A reduced T\u003csub\u003eLCO\u003c/sub\u003e below 70% pred. was noted in 94 (74%) patients (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePulmonary function tests in PLCH patients.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eFVC% pred. (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eALL\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIPLCH\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMS-PLCH\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e127\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e87.8\u0026thinsp;\u0026plusmn;\u0026thinsp;20.5\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e92\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e89.9\u0026thinsp;\u0026plusmn;\u0026thinsp;20.3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e82.2\u0026thinsp;\u0026plusmn;\u0026thinsp;20.2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFEV1% pred. (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e127\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e65.7\u0026thinsp;\u0026plusmn;\u0026thinsp;18.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e67.2\u0026thinsp;\u0026plusmn;\u0026thinsp;20.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e61.6\u0026thinsp;\u0026plusmn;\u0026thinsp;14.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.34\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFEV1%/VC (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e127\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e75\u0026thinsp;\u0026plusmn;\u0026thinsp;18.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e75.4\u0026thinsp;\u0026plusmn;\u0026thinsp;19.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e74\u0026thinsp;\u0026plusmn;\u0026thinsp;18.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.67\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTCL% pred. (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e124\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e104\u0026thinsp;\u0026plusmn;\u0026thinsp;17.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e104.8\u0026thinsp;\u0026plusmn;\u0026thinsp;18.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e101.8\u0026thinsp;\u0026plusmn;\u0026thinsp;14.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.39\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRV% pred. (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e124\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e134.3\u0026thinsp;\u0026plusmn;\u0026thinsp;45.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e132.6\u0026thinsp;\u0026plusmn;\u0026thinsp;44.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e138.8\u0026thinsp;\u0026plusmn;\u0026thinsp;49.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.72\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTL\u003c/b\u003e\u003csub\u003e\u003cb\u003eCO\u003c/b\u003e\u003c/sub\u003e\u003cb\u003e% pred. (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e127\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e58.0\u0026thinsp;\u0026plusmn;\u0026thinsp;16.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e58.5\u0026thinsp;\u0026plusmn;\u0026thinsp;16.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e56.8\u0026thinsp;\u0026plusmn;\u0026thinsp;17.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.47\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFVC% \u0026lt; 70% pred.\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e23 (18%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16 (17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7 (20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.934\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFEV1% \u0026lt; pred. 70%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e60 (47%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44 (48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e16 (48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.989\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFEV1%/VC\u0026thinsp;\u0026lt;\u0026thinsp;70% pred.\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e48 (38%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35 (38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13 (38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.911\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTCL% \u0026lt; 80% pred.\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e7 (6%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.714\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTCL% \u0026gt; 120% pred.\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e20 (16%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5 (15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.968\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRV% \u0026lt; 80% pred.\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e7 (6%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.715\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRV% \u0026gt; 120% pred.\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e73 (59%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e54 (60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e19 (56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.986\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTL\u003c/b\u003e\u003csub\u003e\u003cb\u003eCO\u003c/b\u003e\u003c/sub\u003e \u003cb\u003e\u0026lt; 70% pred.\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e94 (74%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eFEV\u003csub\u003e1\u003c/sub\u003e, forced expiratory volume in 1 s\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eFVC, forced vital capacity\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eHRCT, high-resolution computed tomography\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eIPLCH, isolated pulmonary Langerhans cell histiocytosis\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eMS-PLCH, multisystem Langerhans cell histiocytosis with lung involvement\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003ePLCH, pulmonary Langerhans cell histiocytosis\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003epred., predicted\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eRV, residual volume\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eSD, standard deviation\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eTLC, total lung capacity\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eTL\u003csub\u003eCO\u003c/sub\u003e, diffusion lung capacity for carbon monoxide\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eA negative correlation was found between the incidence of cysts and FEV1% pred. (R=-0.408; p\u0026thinsp;=\u0026thinsp;0.0000), FEV1%/VC ratio (R=-0.343; p\u0026thinsp;=\u0026thinsp;0.0001), and FVC% pred. (R=-0.262; p\u0026thinsp;=\u0026thinsp;0.0029). In contrast, there was a positive relationship between the incidence of cysts and the RV% pred. (R\u0026thinsp;=\u0026thinsp;0.378; p\u0026thinsp;=\u0026thinsp;0.0000). There was no correlation between TLC% pred. and the intensity of the presence of cysts. Moreover, a negative correlation between the incidence of cysts and TL\u003csub\u003eco\u003c/sub\u003e (R=-0.540; p\u0026thinsp;=\u0026thinsp;0.0000) was shown. There were no correlations between the intensity of nodules and pulmonary function tests.\u003c/p\u003e \u003cp\u003eA significantly greater mean cystic score was found in patients with airway obstruction than in patients without airway obstruction (14.76\u0026thinsp;\u0026plusmn;\u0026thinsp;6.30 vs. 10.04\u0026thinsp;\u0026plusmn;\u0026thinsp;6.29; p\u0026thinsp;=\u0026thinsp;0.0000), and the mean intensity of nodules in these patients was lower than that in patients without obstruction (3.54\u0026thinsp;\u0026plusmn;\u0026thinsp;3.20 vs. 5.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.46; p\u0026thinsp;=\u0026thinsp;0.0198).\u003c/p\u003e \u003cp\u003eIn patients with signs of restriction, there was no correlation with the intensity of the cysts or nodules.\u003c/p\u003e \u003cp\u003eThere were no differences between patients with multisystem and isolated PLCH in terms of pulmonary function parameters.\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e\n\u003ch3\u003eMultivariate analysis of the relationship between IPLCH and MS-PLCH groups\u003c/h3\u003e\n\u003cp\u003eIn the multivariate analysis of the relationship between the IPLCH and MS-PLCH patient following factors were considered: gender, cigarette smoking, severity of nodular lesions, and severity of cystic lesions. It was found that cigarette smoking and the severity of cystic lesions, with a probability of 79.5%, classified patients as IPLCH, and with a probability of 20.5% to the MS-PLCH group. In contrast, patients categorized based on selected characteristics into the MS-PLCH group actually came from the IPLCH group with a probability of 11.1% (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u003cb\u003eAnalysis of the probability of belonging to the group of IPLCH or MS-PLCH\u003c/b\u003e\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eDistortion table\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAssigned group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAssigned group\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0,0000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ek\u0026thinsp;=\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIPLCH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMS-PLCH\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReal group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIPLCH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReal group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMS-PLCH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eProbability table\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAssigned group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAssigned group\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIPLCH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMS-PLCH\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReal group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIPLCH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e98,9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,1%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReal group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMS-PLCH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabb\" border=\"1\"\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eReliability table\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eReal group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReal group\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIPLCH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMS-PLCH\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAssigned group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIPLCH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e79,5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20,5%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAssigned group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMS-PLCH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11,1%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e88,9%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eIPLCH, isolated pulmonary Langerhans cell histiocytosis\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eMS-PLCH, multisystem Langerhans cell histiocytosis with lung involvement\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e.\u003c/p\u003e\n\u003ch3\u003eAnalysis% pred.ents with a history of pneumothorax\u003c/h3\u003e\n\u003cp\u003eIn PLCH patients, a negative correlation between age and the occurrence of pneumothorax (p\u0026thinsp;\u0026lt;\u0026thinsp;0.00001) was shown. Moreover, men suffered from pneumothorax more often than women did (36% vs. 18%; p\u0026thinsp;=\u0026thinsp;0.029), and patients with MS-PLCH were more likely to have pneumothorax than patients with IPLCH (51% vs. 46%; p\u0026thinsp;=\u0026thinsp;0.0002). Patients with pneumothorax smoked fewer cigarettes than patients without this symptom (10.27\u0026thinsp;\u0026plusmn;\u0026thinsp;8.59 vs. 21.04\u0026thinsp;\u0026plusmn;\u0026thinsp;17.87 packs/year; p\u0026thinsp;=\u0026thinsp;0.006). Among patients with pneumothorax, the presence of nodules (94% vs. 66%; p\u0026thinsp;=\u0026thinsp;0.001) and cysts (94% vs. 87%; p\u0026thinsp;=\u0026thinsp;0.006) was more common than in patients without pneumothorax. There was no correlation between the cystic score or the nodule score and the occurrence of pneumothorax. The group of patients with pneumothorax did not differ from the group without pneumothorax in terms of the presence of emphysema or cysts (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e). This means that people who developed pneumothorax were younger, smoked less tobacco, were male, and suffered from MS-PLCH more often.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAnalysis of patients with pneumothorax in comparison with those without a history of this condition.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePatients number\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePatients without pneumothorax\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePatients with pneumothorax\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e129 (100%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95 (74%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34 (26%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003cp\u003e(mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39.1\u0026thinsp;\u0026plusmn;\u0026thinsp;14.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40.69\u0026thinsp;\u0026plusmn;\u0026thinsp;14.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28.62\u0026thinsp;\u0026plusmn;\u0026thinsp;9.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.00001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWomen\u003c/p\u003e \u003cp\u003eMen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68 (53%)\u003c/p\u003e \u003cp\u003e61 (47%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56 (82%)\u003c/p\u003e \u003cp\u003e39 (64%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (18%)\u003c/p\u003e \u003cp\u003e22 (36%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.029\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIPLCH\u003c/p\u003e \u003cp\u003eMS-PLCH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e94 (73%)\u003c/p\u003e \u003cp\u003e35 (27%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e78 (54%)\u003c/p\u003e \u003cp\u003e17 (49%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16 (46%)\u003c/p\u003e \u003cp\u003e18 (51%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.0002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking (pack/years) (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18.5\u0026thinsp;\u0026plusmn;\u0026thinsp;16.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.04\u0026thinsp;\u0026plusmn;\u0026thinsp;17.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.27\u0026thinsp;\u0026plusmn;\u0026thinsp;8.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMarijuana smoking\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (13%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (11%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (24%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.148\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCysts score\u003c/p\u003e \u003cp\u003e(mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.9\u0026thinsp;\u0026plusmn;\u0026thinsp;6.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.56\u0026thinsp;\u0026plusmn;\u0026thinsp;6.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.0\u0026thinsp;\u0026plusmn;\u0026thinsp;6.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.237\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNodules score (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.75\u0026thinsp;\u0026plusmn;\u0026thinsp;3.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.56\u0026thinsp;\u0026plusmn;\u0026thinsp;2.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.119\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCysts\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e115 (89%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e83 (87%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32 (94%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmall intensity of cysts\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33 (26%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27 (28%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (18%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.314\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedium intensity of cysts\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38 (29%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (29%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (29%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.837\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh intensity of cysts\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33 (26%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (24%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (29%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.862\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVery high intensity of cysts\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (19%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (18%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (24%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.859\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEmphysema\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40 (31%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (32%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (29%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.816\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of patients with nodules\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e95\u0026nbsp;(73%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63 (66%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32 (94%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eIPLCH, isolated pulmonary Langerhans cell histiocytosis\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eMS-PLCH, multisystem Langerhans cell histiocytosis with lung involvement\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn patients with PLCH, chest CT findings play a key role not only in guiding the diagnosis but also, in many cases, it is a basis for it. The disease is on a spectrum of smoking-related diseases, and despite lesions characteristic of PLCH, lesions characteristic of other diseases can be present.\u003c/p\u003e \u003cp\u003eIn this study, we evaluated these disease-specific radiological lesions in a large group of PLCH patients. No variations in sex, age, smoking habits, or other demographic parameters were observed in our patients in comparison to previously presented patients [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan additionalcitationids=\"CR8 CR9 CR10 CR11\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOwing to the often asymptomatic course of the disease (approximately 30%), nonspecific and poorly expressed symptoms, which are downplayed, especially by young people, a relatively significant diagnostic delay is observed. In addition, the fact that the chest radiograph, sometimes assessed as normal, often affects the prolongation of diagnosis. This situation was present in both the studied group, the European [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] and Chinese [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] populations, and was 18.8, 24, and 17 months long, respectively.\u003c/p\u003e \u003cp\u003ePneumothorax is a characteristic symptom of cystic lung diseases and is the first symptom in 11.7\u0026ndash;25% of PLCH patients [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Moreover, pneumothorax is more common in younger patients, those who smoke less, men, and those with multisystem disease [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSimilar observations regarding radiological findings were published by Kim et al. [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] in a group of 27 PLCH patients. In these studies, nodules and cysts were the most common radiological lesions observed in 89% and 82% of patients, respectively, whereas reticular lesions were present in 19% of patients. Elia et al., in a group of 40 PLCH patients, visualized cysts in 63% of patients, whereas nodules were observed in only 23% of patients [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. In a study by Miao et al., cysts and nodules were observed in 51% and 46% of 109 patients with PLCH, respectively [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. In 112 patients with PLCH reported by Hazim et al., cysts and nodules were observed in 67% and 33% of patients, respectively [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Benattia et al., in a group of 196 patients, presented that 90% of them exhibited a nodulo-cystic pattern of lesions [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe occurrence of emphysema and reticular and honeycomb lesions in PLCH patients was analysed by Koyama et al. [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. These authors reported emphysema in 5 of 18 patients, reticular lesions, and honeycomb lesions in two and one patient, respectively. Ground glass opacities were visualized in 58% of Japanese patients and in 3 out of 14 patients by Vassallo et al. [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Bronchiectasis in those studies was observed in 6% and 8% of patients. A detailed evaluation of the nature of the cystic lesions in the present study revealed that thin-walled cysts were the most common (89% of patients). Thick-walled cysts were detected in 43% of the patients, and sinusoidal cysts were detected in 60% of the patients. There are isolated publications in the available literature that evaluate in detail the nature of cysts in PLCH. Kim et al. visualized thin-walled cysts in 82% of 27 patients, thick-walled cysts in 82%, and sinusoidal cysts less frequently in only 41% of patients [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In contrast, Rodrigues et al., in a group of 8 patients, imaged thick-walled cysts in half of the patients [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. In the present group of patients, nodules\u0026thinsp;\u0026lt;\u0026thinsp;5 mm in diameter were the most common (74%). Nodules between 5\u0026ndash;10 mm and \u0026gt;\u0026thinsp;10 mm in diameter were detected in 24% and 2% of patients, respectively. Quantitative evaluation of the morphological changes among the studied patients revealed that the mean intensity of the nodules was lower than that of the cysts (4.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.4 vs. 11.9\u0026thinsp;\u0026plusmn;\u0026thinsp;6.7). These results were similar to those reported by Tazi et al., who reported that, in a group of 49 patients, the mean intensities of nodular and cystic lesions were 6.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.4 and 11.9\u0026thinsp;\u0026plusmn;\u0026thinsp;6.1, respectively [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], but in a recent data from this group mean nodular score was 6.8, and mean cystic score was also 6.8 [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In a group of 196 patients, Benattia et al. reported that HRCT cystic scores were predominantly low to intermediate in 175 patients (89.3%), potentially indicating an earlier stage of the disease [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In our patient cohort, this scoring pattern was observed in 55% of individuals, indicating that our patients had more advanced stages of the disease. This phenomenon can be attributed to disease progression, where initial nodular lesions are more prevalent, followed by the development of cavitary nodules and, eventually, the emergence of thick- and thin-walled cysts. The extended period before diagnosis contributes to patients presenting with more advanced disease [\u003cspan additionalcitationids=\"CR8 CR9\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRecently, Poellinger et al. described a specific new \u0026ldquo;octopus sign\u0026rdquo; in the radiological presentation of PLCH patients. It corresponds to small septal fibrotic strands emanating from a central bronchiolocentric scar that form a typical appearance resembling a star. It is suggested that the octopus sign could be helpful to differentiate between certain stages of LCH and centrilobular emphysema [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Our study was performed earlier, and this sign was not assessed.\u003c/p\u003e \u003cp\u003eNumerous publications emphasize the fact that the disease spares the supradiaphragmatic parts of the lungs. In a publication by Elia et al., the lower parts of the lungs were spared in 62% of patients [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Vassallo et al. reported a predominance of lesions in the upper and middle portions of the lungs in 18 of 29 patients [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In contrast, Kim et al. reported lower lung lesions in only 3 of 27 patients [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. However, these analyses were quite general. In our study, in 50% of the patients, both the anterior and posterior parts of the lung base, i.e., the free basal parts of the middle lobe and lingula, were free from lesions, as were the free basal parts of the lower lobes. In addition, quite often, only the anterior parts were free of lesions (19%). Lesion-free only basal parts of the lower lobes of the lungs were observed in a small percentage (5%) of patients. The involvement of all supradiaphragmatic portions of the lungs was visualized in 26% of the PLCH patients. This detailed analysis is presented for the first time.\u003c/p\u003e \u003cp\u003eHilar and mediastinal lymphadenopathy is not a highly characteristic feature among adult PLCH patients and has been demonstrated in 6\u0026ndash;20% of presented patients [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMean values of pulmonary function tests observed in our group were like to those previously published [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan additionalcitationids=\"CR30\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. In addition, there was a negative correlation between the incidence of cysts and FEV1% pred. (p\u0026thinsp;=\u0026thinsp;0.0000), FEV1%/VC ratio (p\u0026thinsp;=\u0026thinsp;0.0001), FVC% pred. (p\u0026thinsp;=\u0026thinsp;0.0029), and TL\u003csub\u003eco\u003c/sub\u003e% pred. (p\u0026thinsp;=\u0026thinsp;0.0000), and a positive correlation between RV% pred. (p\u0026thinsp;=\u0026thinsp;0.0000). The relationship between radiological images and functional tests has also been presented by other authors. Canuet et al. reported an association between the incidence of cysts and the FEV1/VC ratio (p\u0026thinsp;=\u0026thinsp;0.01) and TL\u003csub\u003eco\u003c/sub\u003e (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) in 26 PLCH patients [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Tazi et al., in a retrospective analysis of 49 patients, did not detect a significant correlation between the intensity of nodules incidence and lung ventilation parameters. In contrast, the degree of cyst presence was strongly correlated with a decrease in the FEV1%, FEV1%/VC ratio (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) and TL\u003csub\u003eco\u003c/sub\u003e % pred. (p\u0026thinsp;=\u0026thinsp;0.01) [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. These observations support the fact that patients with a predominant pattern of nodular changes on CT scans are in the early stages of PLCH, with few consequences for their respiratory parameters.\u003c/p\u003e \u003cp\u003eThe focus of this study was the evaluation of findings visualized by HRCT in PLCH patients and to analyse differences in radiological presentation between patients with isolated and multisystem PLCH.\u003c/p\u003e \u003cp\u003eWe presented that IPLCH patients did not differ from MS-PLCH patients in the degree of functional lung damage, impaired carbon monoxide transfer factor. The above observations are unique and have not been reported in the literature.\u003c/p\u003e \u003cp\u003eAnother issue not previously analysed in the literature was an attempt to answer the question of whether there are radiological and/or clinical factors to differentiate the group of patients with IPLCH from those with MS-PLCH. The fact of higher smoking intensity and lower severity of cystic lesions was associated with a higher probability of isolated lung involvement. It was determined that patients with a probability of 79.5% classified as IPLCH actually came from this group, and with a probability of 20.5% from the MS-PLCH group. In contrast, patients classified on the basis of selected characteristics into the MS-PLCH group were actually from the IPLCH group with a probability of 11.1%.\u003c/p\u003e \u003cp\u003eThe algorithm used in this analysis for the IPLCH and MS-PLCH patient groups could be applied to the work of radiologists and clinicians, helping predict the extent of the disease.\u003c/p\u003e \u003cp\u003eA limitation of the study is that it was a retrospective, single-center study. However, this was one of the largest analysed populations of histologically confirmed PLCH patients, and the study was performed at the Expert Center for Rare Diseases, which belongs to the ERN-LUNG.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCOPD, chronic obstructive pulmonary disease\u003c/p\u003e\n\u003cp\u003eGERD, gastroesophageal reflux disease\u003c/p\u003e\n\u003cp\u003eFEV\u003csub\u003e1\u003c/sub\u003e, forced expiratory volume in 1 s\u003c/p\u003e\n\u003cp\u003eFVC, forced vital capacity\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHRCT, high-resolution computed tomography\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIPLCH , isolated pulmonary Langerhans cell histiocytosis\u003c/p\u003e\n\u003cp\u003eMRI,\u003c/p\u003e\n\u003cp\u003eMS-PLCH , multisystem Langerhans cell histiocytosis with lung involvement\u003c/p\u003e\n\u003cp\u003ePaO\u003csub\u003e2\u003c/sub\u003e, partial pressure of oxygen in the blood\u003c/p\u003e\n\u003cp\u003ePaCo2, partial pressure of carbon dioxide in the blood\u003c/p\u003e\n\u003cp\u003ePLCH , pulmonary Langerhans cell histiocytosis\u003c/p\u003e\n\u003cp\u003epred., predicted\u003c/p\u003e\n\u003cp\u003eRV, residual volume\u003c/p\u003e\n\u003cp\u003eSD, standard deviation\u003c/p\u003e\n\u003cp\u003eTLC, total lung capacity\u003c/p\u003e\n\u003cp\u003eTL\u003csub\u003eCO\u003c/sub\u003e, diffusion lung capacity for carbon monoxide\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by\u0026nbsp;the National Tuberculosis and Lung Diseases Ethics Committee (No. KB-11/2019).\u003c/p\u003e\n\u003cp\u003eAll patients provided written informed consent for the use of their medical records for research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe other editorial board does not consider the article.\u003c/p\u003e\n\u003cp\u003eAll authors approved this manuscript and declared no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll source data are available on request\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declared no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Internal Review Board of the National Tuberculosis and Lung Disease Institute and was supported by the grant No. 7.33/2018.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStudy conception and design: ER, MJ, IB. Acquisition of data: ER, MS, JM-D, RL, SW, WN, DJ, WK. Assessment of radiological findings: MJ, KB, IB, KO, BB, JW. Analysis of data, drafting, and writing of the manuscript [ER, MJ, IB]. All authors contributed to reviewing the manuscript and approved the final version for publication\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGoyal G, Tazi A, Go RS, et al. International expert consensus recommendations for the diagnosis and treatment of Langerhans cell histiocytosis in adults. Blood. 2022;139:2601\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGirschikofsky M, Arico M, Castillo D, et al. Management of adult patients with Langerhans cell histiocytosis: recommendations from an expert panel on behalf of Euro-Histio-Net. Orphanet J Rare Dis. 2013;8:72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAric\u0026ograve; M, Girschikofsky M, G\u0026eacute;n\u0026eacute;reau T, et al. 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Respiration. 2007;74:640\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"orphanet-journal-of-rare-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ojrd","sideBox":"Learn more about [Orphanet Journal of Rare Diseases](http://ojrd.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ojrd/default.aspx","title":"Orphanet Journal of Rare Diseases","twitterHandle":"@bmc","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"multisystem Langerhans cell histiocytosis, isolated pulmonary Langerhans cell histiocytosis, cystic lung diseases, nodules, cavitary nodules","lastPublishedDoi":"10.21203/rs.3.rs-9357366/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9357366/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003ePulmonary Langerhans cell histiocytosis (PLCH) is characterized by the proliferation of cells affected by mutations in genes related to the mitogen-activated kinase pathway. The lungs can be involved as an isolated organ (IPLCH) or as one of the others (MS-PLCH). High-resolution computed tomography (HRCT) and pulmonary function tests play crucial roles in the diagnosis and assessment of its activity. This study aimed to evaluate radiological findings in PLCH patients and determine their correlation with the extent of the disease and pulmonary function.\u003c/p\u003e \u003cp\u003eMaterial: This study evaluated 129 (53% women) PLCH patients, 96% of whom were smokers, with a mean age of 39.1\u0026thinsp;\u0026plusmn;\u0026thinsp;14.1 years, who were hospitalized at the NTLDI in Warsaw between 2007 and 2021.\u003c/p\u003e \u003cp\u003eResults: Cysts (89%), nodules (73%), emphysema (31%), reticular lesions (22%), cavitary nodules (21%), lymphadenopathy (16%), ground glass opacities (11%), dilatation of the pulmonary artery trunk (9%), bronchiectasis (7%), and honeycomb changes (1%) were visualized via HRCT. A negative correlation between the severity of cysts and nodules was found (p\u0026thinsp;=\u0026thinsp;0.0002). A negative correlation between the intensity of the cysts and the FVC% pred. (p\u0026thinsp;=\u0026thinsp;0.0029), FEV1% pred. (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0000), FEV1%/VC (p\u0026thinsp;=\u0026thinsp;0.0001), and TLco (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0000) was shown. Higher intensity of smoking and greater severity of cysts classified patients as IPLCH with a 79.5% probability.\u003c/p\u003e \u003cp\u003eConclusions: Cysts, cavitary nodules, and nodules have been identified as the most frequent radiological findings in PLCH patients. The negative correlation between the severity of cysts and FVC% pred., FEV1% pred., and TLco% pred. was found. The higher severity of cysts and intensity of smoking discriminated patients with IPLCH from those with MS-PLCH.\u003c/p\u003e","manuscriptTitle":"Lung structure disorders visualized by chest computed tomography in patients with pulmonary Langerhans cell histiocytosis and their correlation with the pulmonary function tests and disease extension","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-15 18:50:21","doi":"10.21203/rs.3.rs-9357366/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"43090071420848513096894349953842908885","date":"2026-05-06T13:15:04+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-05-06T13:01:13+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-10T09:32:34+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-10T09:31:35+00:00","index":"","fulltext":""},{"type":"submitted","content":"Orphanet Journal of Rare Diseases","date":"2026-04-08T12:56:32+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"orphanet-journal-of-rare-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ojrd","sideBox":"Learn more about [Orphanet Journal of Rare Diseases](http://ojrd.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ojrd/default.aspx","title":"Orphanet Journal of Rare Diseases","twitterHandle":"@bmc","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"93cdfcb3-5958-435a-bcaa-1bd029dc8533","owner":[],"postedDate":"May 15th, 2026","published":true,"recentEditorialEvents":[{"type":"reviewerAgreed","content":"43090071420848513096894349953842908885","date":"2026-05-06T13:15:04+00:00","index":17,"fulltext":""},{"type":"reviewersInvited","content":"7","date":"2026-05-06T13:01:13+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-15T18:50:21+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-15 18:50:21","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9357366","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9357366","identity":"rs-9357366","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}