Evaluation of Pulmonary and Otological Manifestations in Primary Ciliary Dyskinesia and Their Effect on Quality of Life

Objective: Otitis media and conductive hearing loss are common in patients with primary ciliary dyskinesia (PCD). We aimed to assess the pulmonary, ear-nose-throat, and otologic features of individuals with PCD and their effect on quality of life (QOL).

Demographic data, spirometry values, a health-related quality of life questionnaire for PCD patients (QOL-PCD), physical examination data of sinonasal and otologic systems, the sinonasal outcome test-22, and audiologic tests were recorded in this prospective, and cross-sectional study. The pure tone audiometry, distortion product otoacoustic emission (DPOAE), tympanogram, and the Turkish matrix test (TUR-matrix) evaluating speech understanding in noise were performed.Results: Fifty-six patients with PCD were included in the study. The scores of the social, upper, and lower respiratory domains of the QOL-PCD were significantly lower in adults than in children and adolescents (p-value <0.001, 0.02, and 0.01, respectively).The hearing and the TUR-matrix were pathologic in 26 (46.4%) and 36 (64.3%) cases, respectively. Patients with pathological hearing had significantly worse results in regards to the FEV1 z-score (-1.7 vs. -0.8, p=0.01), the TUR-matrix test (20 vs 16 cases, p=0.001), the DPOAE (25 vs 11 cases, p<0.001), and the tympanogram (26 vs 12 cases, p<0.001) than patients with normal hearing. Conclusion: Sinopulmonary involvement and hearing manifestations are very common in patients with PCD, and speech understanding in noise is often impaired. These manifestations impact QOL in various areas. Evaluation of Pulmonary and Otological Manifestations in Primary Ciliary Dyskinesia and Their Effect on Quality of Life Muruvvet Yanaz1, [email protected] Ela Erdem Eralp1, [email protected] Cansu Yilmaz Yegit1, [email protected] Aynur Gulieva1, [email protected] Mine Kalyoncu1, [email protected] Merve Selcuk Balci1, [email protected] Seyda Karabulut1, [email protected] Nuru Aliyev2, [email protected] Nezafet Ozturk3, [email protected] Almala Pınar Ergenekon1, [email protected] 1 Posted on 22 May 2025 | The copyright holder is the author/funder. All rights reserved. No reuse without permission. | https://doi.org/10.22541/au.174789764.47378366/v1 | This is a preprint and has not been peer-reviewed. Data may be preliminary. Yasemin Gokdemir1, [email protected] Ali Cemal Yumusakhuylu2, [email protected] Ayca Ciprut3, [email protected] Bulent Karadag1, [email protected] 1 Marmara University School of Medicine, Division of Pediatric Pulmonology 2 Marmara University School of Medicine, Department of Otolaryngology 3 Marmara University School of Medicine, Department of Audiology Correspondence to: Muruvvet Yanaz, MD Division of Pediatric Pulmonology Marmara University, School of Medicine Address: Fevzi ¸ Cakmak mahallesi, Muhsin Yazıcıo˘ glu caddesi, No:10, 34899, Pendik/Istanbul, TURKIYE Tel (mobile): +905364191641 Fax: +902166254639 Email: [email protected] Ethical statement: The study was approved by the Ethical Committee of Marmara University School of Medicine (protocol number: 09.2022.498). Conflict of interest:None Author contributions: Data curation: Muruvvet Yanaz, Ela Erdem Eralp, Almala Pinar Ergenekon, Ali Cemal Yumu¸ sakhuylu, Yasemin Gokdemir, Ayca Ciprut, Bulent Karadag.Conceptualization: Muruvvet Yanaz, Ela Erdem Er- alp, Almala Pinar Ergenekon, Ali Cemal Yumu¸ sakhuylu, Yasemin Gokdemir, Ayca Ciprut, Bulent Karadag. Formal analysis:Muruvvet Yanaz.Investigation: Muruvvet Yanaz, Cansu Yilmaz Yegit, Aynur Gulieva, Mine Kalyoncu, Merve Selcuk Balci, Seyda Karabulut, Nuru Aliyev, Nezafet Ozturk.Methodology: Mu- ruvvet Yanaz, Ela Erdem Eralp, Almala Pinar Ergenekon, Ali Cemal Yumu¸ sakhuylu, Yasemin Gokdemir, Ayca Ciprut, Bulent Karadag. Resources: Muruvvet Yanaz, Cansu Yilmaz Yegit, Aynur Gulieva, Mine Kalyoncu, Merve Selcuk Balci, Seyda Karabulut, Nuru Aliyev, Nezafet Ozturk. Visualization: Mu- ruvvet Yanaz. Writing-original draft: Muruvvet Yanaz, Mine Kalyoncu, Nezafet Ozturk. Writing- review & editing:Ela Erdem Eralp, Almala Pinar Ergenekon, Yasemin Gokdemir, Ayca Ciprut, Bulent Karadag.Supervision: Ela Erdem Eralp, Almala Pinar Ergenekon, Ali Cemal Yumu¸ sakhuylu, Yasemin Gokdemir, Ayca Ciprut, Bulent Karadag. Financial support: None

Primary ciliary dyskinesia, quality of life, hearing, speech understanding in noise

Objective: Otitis media and conductive hearing loss are common in patients with primary ciliary dyskinesia (PCD). We aimed to assess the pulmonary, ear-nose-throat, and otologic features of individuals with PCD and their effect on quality of life (QOL).

Demographic data, spirometry values, a health-related quality of life questionnaire for PCD patients (QOL-PCD), physical examination data of sinonasal and otologic systems, the sinonasal outcome test-22, and audiologic tests were recorded in this prospective, and cross-sectional study. The pure tone 2 Posted on 22 May 2025 | The copyright holder is the author/funder. All rights reserved. No reuse without permission. | https://doi.org/10.22541/au.174789764.47378366/v1 | This is a preprint and has not been peer-reviewed. Data may be preliminary. audiometry, distortion product otoacoustic emission (DPOAE), tympanogram, and the Turkish matrix test (TUR-matrix) evaluating speech understanding in noise were performed.

Fifty-six patients with PCD were included in the study. The scores of the social, upper, and lower respiratory domains of the QOL-PCD were significantly lower in adults than in children and adolescents (p- value <0.001, 0.02, and 0.01, respectively).The hearing and the TUR-matrix were pathologic in 26 (46.4%) and 36 (64.3%) cases, respectively. Patients with pathological hearing had significantly worse results in regards to the FEV1z-score (-1.7 vs. -0.8, p=0.01), the TUR-matrix test (20 vs 16 cases, p=0.001), the DPOAE (25 vs 11 cases, p<0.001), and the tympanogram (26 vs 12 cases, p<0.001) than patients with normal hearing.

Sinopulmonary involvement and hearing manifestations are very common in patients with PCD, and speech understanding in noise is often impaired. These manifestations impact QOL in various areas.

Primary ciliary dyskinesia (PCD) is a rare autosomal recessive genetic disease that affects cilia structure and function1,2. This condition impairs mucociliary clearance, leading to a spectrum of oto-sino-pulmonary manifestations. Patients commonly experience upper and lower respiratory tract infections, bronchiectasis, otitis media with effusions (OME), rhinitis, chronic rhinosinusitis, and hearing loss (HL)3,4. Moreover, all forms of otitis media and mild to moderate conductive HL are common in patients with PCD, and some of them may also have sensorineural HL5. Chronic middle ear effusion may lead to behavioral and speech development issues, according to data from other circumstances6,7. Recently, research in PCD has focused on pulmonary findings, but the data on upper airway disease and otological findings is scarce8,9. Findings of the existing research vary because most of the studies are single- centered, retrospectively designed, have a small number of participants, and consist primarily of pediatric patients10,11.There is also high heterogeneity in outcome measures10. Additionally, the degree to which the disease affects various organ systems may have an impact on a patient’s quality of life (QOL) in different areas12,13. In this study, we aimed to assess the pulmonary, ear-nose-throat (ENT), and otologic features of individuals with PCD and their effect on QOL.

Study design and patient selection We performed a prospective and cross-sectional study between January 2023 and January 2024, including all patients above six years of age with either a confirmed or highly likely diagnosis of PCD according to the European Respiratory Society14. According to this guideline, those with bi-allelic pathogenic variants in PCD-related genes or hallmark defects on transmission electron microscopy were considered confirmed cases, and those with very low nasal nitric oxide plus high-speed videomicroscopy analysis findings consistent with PCD on three occasions were considered to have a highly likely diagnosis. We had 87 patients with PCD. Fourteen were excluded because they were younger than six years old. The remaining 73 patients were invited for participation. Written informed consent was obtained from all participants. The study was approved by the Ethical Committee of Marmara University School of Medicine (protocol number: 09.2022.498). Pulmonary evaluation Demographic data including clinical manifestations of PCD, spirometry measurements and microbiological findings of the patients were recorded. Pseudomonas aeruginosa (PA) colonization was assessed based on the Leeds criteria, which defines colonization as the presence of PA in more than 50% of the cultures obtained 3 Posted on 22 May 2025 | The copyright holder is the author/funder. All rights reserved. No reuse without permission. | https://doi.org/10.22541/au.174789764.47378366/v1 | This is a preprint and has not been peer-reviewed. Data may be preliminary. within the past year15. The severity of the spirometry was defined based on the z-score according to the American Thoracic Society/European Respiratory Society statement as below: mild –1.65 to –2.5, moderate –2.51 to –4.0,and severe < –4.116. The participants and parents of patients aged six to 12 years were asked to perform a validated health-related quality of life questionnaire for PCD patients (QOL-PCD)17. It includes four different questionnaires for children (6–12 years), teenagers (13–17 years), adults (18+ years), and parents of children aged from six to 12 years, and higher scores mean better results. The questions included the following domains depending on age: respiratory symptoms, physical functioning, emotional functioning, treatment burden, ears and hearing, sinus symptoms, social functioning, role functioning, vitality, health perceptions, school functioning, and eating and weight. ENT evaluation The ENT department of our hospital performed a detailed examination of the upper airways and ear and the Sino-Nasal Outcome Test 22 (SNOT-22) on the same day as pulmonary evaluation18. SNOT-22 is a validated, patient-based QOL questionnaire and measures sino-nasal symptoms. The theoretical score runs from 0 to 110, and higher scores suggest a worse QOL and correspond to a mild (0-20), moderate (21-50), or severe ([?]51) effect of chronic rhinosinusitis on QOL. Nine patients were excluded, because they did not want to participate due to long waiting times. To minimize potential bias in our evaluation of hearing loss, patients within their baseline state of health were referred for audiological assessment. Participants with an active upper respiratory tract infection were not referred for audiological assessment until six weeks after they returned to baseline status. This approach helped to avoid transient hearing impairments related to acute infections, ensuring that audiological findings more accurately reflected the patients’ chronic condition rather than temporary inflammatory changes. Audiological evaluation The hearing was evaluated by pure-tone audiometry, speech audiometry, acoustic immitancemetry, and otoacoustic emissions within a maximum of two weeks after the ENT in 56 participants, because eight of them did not come to their appointments. All participants were evaluated with an AC-40 clinical audiometer (interacoustics A/S, AudiometerAlle 1, 5500 Middelfart, Denmark) and JBL Speaker System (JBL, Harman International, USA) in a soundproof booth. All participants completed an audiological evaluation consisting of air- and bone-conducted pure-tone thresholds (0.25 to 8 kilohertz-kHz- octave frequencies for air conduction; 0.5 to 4 kHz for bone conduction) for both ears using the American Speech and Hearing Association guidelines19. The pure tone average (PTA) on four frequencies (0.5, 1, 2, and4 kHz) was calculated for air and bone conduction. Conductive HL was defined as the PTA exceeding 26 decibels (dB) and the presence of an air-bone gap of 10 dB or more over three of the following frequencies: 500,1000, 2000, and 4000. Speech audiometry was conducted to assess both speech discrimination (SD) score in a quiet environment and the speech reception threshold (SRT). The SRT represents the decibel level at which the subject can correctly repeat 50% of the words presented. Additionally, the SD score of 100% indicates the decibel level at which the subject can repeat all presented phonetically balanced monosyllabic words accurately. Distortion product otoacoustic emission (DPOAE) was examined with the ILO292 USB-I Otoacoustic Emis- sions Instrument (Otodynamics Ltd.Beaconsfield Road Hatfield, AL10 8BB, U.K.). DPOAE responses were considered valid when at least the lowest amplitude of 0 dB was reached and the signal/noise ratio (SNR) was > 6 dB for three frequencies20. Acoustic immittancemetry was examined with an Interacoustics A/S DK-5610 Assens Type 2 impedance audiometer to evaluate outer and middle ear components and included tympanography and ipsilateral and contralateral acoustic reflex tests (0.5- 1-2 kHz). Jerger tympanogram types were used to categorize acoustic immitancemetry results21. All the tympanograms, apart from the type A, were considered pathological. 4 Posted on 22 May 2025 | The copyright holder is the author/funder. All rights reserved. No reuse without permission. | https://doi.org/10.22541/au.174789764.47378366/v1 | This is a preprint and has not been peer-reviewed. Data may be preliminary. SpeechunderstandinginnoisewasdeterminedbytheTurkishMatrixTest(TUR-MatrixTest), andaudiologic spectral resolution ability was evaluated by the spectral-temporally modulated ripple test (SMRT)22,23. The TUR-Matrix test was examined via Otometrics Astera, a GN Otometrics, Taastrup, Denmark audiome- ter. The participants were evaluated at 65 dB SPL using non-adaptive mode; the test aimed to determine the SRT, defined as the signal-to-noise ratio (SNR) at which the participants correctly recognized 50% of the words in the sentences. SMRT is used to assess the ability to discriminate spectral-temporal cues. Higher values indicate better spectral resolution capability in normal-hearing subjects. The mean RPO value was found to be eight23. The SMRT was applied to all participants at 65 dB SPL, 0°azimuth in a soundproof booth. Statistical analysis Only the participants who completed all of the pulmonary, ENT, and audiologic evaluations were analyzed statistically. The IBM SPSS Statistics (version 22.0 IBM Corp., Armonk, NY) software program was used to analyze the data. Categorical variables are presented as numbers (n) and percentages (%). Continuous variables are shown as medians with interquartile range (IQR) for the data that did not follow a normal distribution and are shown as means with standard deviation for the data with a normal distribution. Cate- gorical variables were compared through Pearson’s chi-square and Fisher’s exact tests. Continuous variables for two groups were compared with the Mann-Whitney U test, and for three groups, the Kruskal-Wallis test was performed. The correlation coefficients and their significance were calculated using the Spearman correlation test. A p-value <0.05 was considered significant.

Demographical and clinical findings We had 87 eligible patients with PCD. Of them, 14 were excluded because they were younger than six years old. The remaining 73 patients were invited for participation. Nine patients were excluded, because they did not want to participate due to long waiting times in ENT examination. Fifty-six patients with PCD were included in the study, because eight of them did not come to their audiology appointments. Thirty-one of them (55.4%) were male, and the mean age was 15.2±5.4 years. The median age at diagnosis was 72 months (IQR: 6-140). The median [IQR] FEV1 z-score was -1.5 [-2.3-(-0.2)]. PA colonization was detected in 5 patients (8.9%), and the median (IQR) FEV1 z-score was significantly lower in patients with PA colonization [-2.2 (-4.2- -0.7)] than in patients with no colonization [-1.4 (-2.3-0.2)] (p=0.04). Additional clinical findings of patients with PCD were presented in Table 1. In ENT examination, a blocked nose was detected in 29 patients (51.8%). A total of 41 patients (73.2%) had nasal discharge, and of them, 19 (46.3%) were mucopurulent, 17 (41.5%) were seromucuos, and five (12.2%) had serous nasal discharge. Nasal polyps was detected in five patients (8.9%). Tympanic perforation was detected in five ears of four patients (7.1%). Acute OME was detected in 20 ears of 13 patients (23.2%). Tympanic sclerosis was detected in 10 ears of seven patients (12.5%). A ventilation tube was present in five ears of four patients (7.1%). Additional ENT examination findings of patients with PCD were presented in Table 2. The median (IQR) SNOT-22 scores of all participants was 29.0 (19.0-39.0). The median (IQR) SNOT-22 scores of children, adolescents, and adults were 29.0 (15.0-41.0), 30.0 (22.0-39.0), and 26.0 (16.0- 38.0) respectively (p=0.70). None of the ENT examination findings showed a significant difference between age groups as children, adolescents and adults. Assessment of quality of life The results of QOL-PCD questionnaires for each age group and parents are represented in Table 3. The scores of the social, upper, and lower respiratory domains of the questionnaire were found to be significantly lower in adults than in children and adolescents (p value 5 Posted on 22 May 2025 | The copyright holder is the author/funder. All rights reserved. No reuse without permission. | https://doi.org/10.22541/au.174789764.47378366/v1 | This is a preprint and has not been peer-reviewed. Data may be preliminary. Audiological findings In 26 cases (46.4%), the hearing was confirmed to be pathologic. Eighteen (32.1%) had normal hearing with conductive pathology. Seven patients (12.5%) had at least one ear affected by very mild conductive HL, and one patient (1.8%) had at least one ear affected by mild conductive HL. The median (IQR) PTA for air (PTAAC) and bone conduction (PTABC) were presented in Table 4. The PTAAC was above 26 dB in five ears (8.9%) in the right and six ears (10.7%) in the left; it was pathologic in both ears of two patients (3.6%) and one ear of seven patients (12.5%). The PTA differences were above 10 dB in 22 ears (39.3%) in the right and 24 ears (42.9%) in the left. The median SD scores for the right and left ears were found to be 92.0 (88.0-100.0) and 96.0 (88.0-100.0), respectively. Twenty-two cases (39.3%) had bilateral lower SDS scores than expected for normal hearing and conductive HL according to Jerger classification. One patient had the lowest SD score in both ears (76.0 in the right and 68.0 in the left ear). The median TUR-matrix threshold was found to be -4.3 [-5.5-(-2.4)]; the TUR-matrix was pathologic in 36 patients (64.3%). The median (IQR) SMRT was found to be 7.6 (6.9-8.5). The SMRT results were within normal limits. The tympanogram was normal in 21 cases (37.5%) in the right ear and 23 cases (41.1%) in the left ear. The results of the tympanogram were presented in Table 5. According to DPOAE, the otoacoustic emission could not be detected in 32 ears (57.1%) in the right ear and 34 ears (60.7%) in the left ear. Patients with normal and pathological hearing were compared in Table 6. Patients with pathological hearing had significantly worse results in regards to the FEV1 z-score, the TUR-matrix test, the DPOAE, and the tympanogram (p value 0.01, 0.001, <0.001, and <0.001 respectively). In our cohort, significant correlations were detected among study variables. The SNOT-22 score was signi- ficantly correlated with the physical, emotional, burden, role, social, vitality, and lower respiratory domains of the QOL-PCD (r=-0.413, p=0.002;r=-0.435, p=0.001; r=-0.476, p=0.001; r=-0.407, p=0.01; r=-0.315, p=0.02; r=-0.330, p=0.04; and r=-0.512, p<0.001,respectively).

We present significant findings regarding the clinical characteristics, QOL, and hearing of people with PCD in this study. The hearing was impaired in 46%, and pulmonary functions and speech understanding in noise were worse in people with impaired hearing. Adults showed worse QOL linked to the upper and lower respiratory systems, social interactions, and physical health than children and adolescents. Impaired mucociliary clearance in PCD patients leads to recurrent pulmonary infections and thus bronchiec- tasis, and sputum cultures may contain several bacterial pathogens24. In our study, 75% had bronchiectasis, and PA colonization was detected in 8.9%. FEV1 z-score was lower in patients with PA colonization. In the study of Pifferi et al., which included slightly more adults than our study (27 adults, total 51 PCD pati- ents), bronchiectasis was documented in 86%. Bacterial colonization with PA (alone or associated with other bacteria) was found in 37%, and other organisms were found in 73% of PCD patients. Although bronchiec- tasis and PA colonization ratios were higher than in ours tudy, the mean FEV1z-score was -0.6±1.0, better than in our study25. Similar to our study, in the Boon et al. study, 168 PCD patients were analyzed, with a median age of 17.7 years. They detected bronchiectasis in 68%, and the median FEV1 z-score was -1.8. Bacterial colonization with PA was shown to be associated with loss of lung function26. This emphasizes the importance of regular monitoring pulmonary function and bacterial colonization and appropriate treatment. Pulmonary involvement of patients with PCD is currently managed in the same manner as those with cystic fibrosis and non-cystic fibrosis bronchiectasis9. It is inappropriate to extrapolate data from other diseases since variations in etiology, morbidity, and prognosis increase the chance of treatment failure and noncom- pliance. Randomized clinical trials and prospective studies are needed to shed light on clinical standards and evidence-based guidelines specific to patients with PCD. Patients with PCD frequently experience sinonasal symptoms, which might include rhinorrhea or blocked nose, facial pain, and headaches27. In our study, we detected nasal discharge in 73%, a blocked nose in 52%, 6 Posted on 22 May 2025 | The copyright holder is the author/funder. All rights reserved. No reuse without permission. | https://doi.org/10.22541/au.174789764.47378366/v1 | This is a preprint and has not been peer-reviewed. Data may be preliminary. erythema in 20%, edema in 14%, nasal polyps in 9%, hypertrophic nasal turbinates in 25%, and septum deviation in 68%. Similar to these findings, Lam et al. detected nasal discharge in 73%, blocked nose in 43%, mucosal edema in 28%, nasal polyps in 14%, hypertrophic nasal turbinates in 34%, and deviated septum in 31% in their 12-centered study with 370 PCD patients28. People with PCD may have a lower QOL as a result of these sinonasal and respiratory involvements12,13. In our study, as a result of SNOT-22, the QOL was found to be moderately affected, and the physical, social, upper, and lower respiratory domains of the PCD-QOL were found to be significantly lower in adults than in others. Similar to our findings, in the prospective study of Zawawi et al., they reported a higher mean SNOT-22 score in 47 patients with PCD than healthy controls (36.4 vs 5)8. In the study of Gut et al., the median SNOT-22 score was found to be 35 in 27 PCD patients; in addition to that, they found negative correlations between several PCD-QOL domains and SNOT-22 and the forced oscillation technique, which is a method for measurement of respiratory functions13. In our study, the SNOT-22 was negatively correlated with the physical, emotional, burden, role, social, vitality and lower respiratory domains of the PCD-QOL, and the FEV1 z-score was negatively correlated with PTA results. However, we could not find a correlation with the upper respiratory and hearing domains. This might be due to patients’ underreporting their sinonasal symptoms. Since most PCD symptoms are nonspecific, patients with PCD may learn to cope with their symptoms or consider them unproblematic, and they may neglect their symptoms. According to another study of Lam et al., which included 404 PCD patients from 12 centers with a median age of 15 years, underreporting varied by symptom and was more common for runny (25%) or blocked (23%) noses29. Therefore, patientswith PCD should be assessed with objective tests by ENT specialists routinely. Patients with PCD may experience several otologic manifestations, such as conductive HL and OME, as a

of dysfunctional mucociliary clearance in the middle ears and the Eustachian tube. The prevalence of hearing loss in patients with PCD was detected between 25-75%3,5,30. Similar to the literature, in our study hearing was affected in 46%. Patients who had HL had more abnormal tympanograms and absent otoacoustic emissions. This can be due to the sequelae of otitis media. The fact that some of the PCD patients with normal hearing had abnormal tympanogram findings and absent otoacoustic emissions could indicate the negative impact of otitis media on the middle ear. The conductive HL in these patients can be treated with antibiotics and ventilation tubes; however, it has been shown that normal hearing can be maintained with a conservative observational strategy in some of the children with PCD as age increases31.32. Therefore, different management strategies should be applied on a case-by-case basis. In addition to evaluation of hearing, to our knowledge, this is the first study to assess speech understanding in noise. It was detected as pathologic in nearly 64% of the cases in this study, and the more pathological TUR-matrix results were detected in patients with pathologic hearing. Studies have shown that impairments in auditory input due to OME are linked to impaired function of descending neural pathways and reduced ability to recognize speech in noisy environments33-36. Difficulty in understanding speech in noise can negatively affect daily interactions and hinder communication, especially in educational settings with background noise. Patients with persistent OME may have significant difficulties in understanding teacher and peer speech in noisy classrooms, leading to increased listening effort and fatigue and adecrease in QOL37-38. Likewise, the decrease in speech intelligibility in noise and the low speech discrimination scores in quiet in 22 cases, which are not expected in normal hearing and conductive HL, show the effect of long-lasting otitis on the hearing system. Similarly, in another study, children with unilateral or bilateral OME had a mean increase of 5 dB or 15 dB, respectively, for word recognition thresholds in quiet39. Speech in noise tests can be utilized for PCD patients’ follow-up and treatment planning, because it gives significant and useful results. Additionally, patients with pathologic hearing showed a lower FEV1z-score. In another study of Lam et al., shortness of breath and sputum production were associated with reported nasal symptoms and hearing40. So, we should pay more attention to HL, particularly in patients with low FEV1 or lower respiratory symptoms. This study has some strengths and limitations. Although this is a single-centered and relatively small sample- sized study, the prospective and multidisciplinary design and the fact that the tests have not been performed before in this patient group, such as speech understanding tests, strengthen our study. In conclusion, this study presents a detailed evaluation of patients with PCD by a multidisciplinary approach 7 Posted on 22 May 2025 | The copyright holder is the author/funder. All rights reserved. No reuse without permission. | https://doi.org/10.22541/au.174789764.47378366/v1 | This is a preprint and has not been peer-reviewed. Data may be preliminary. with a team of pediatric pulmonologists, ENT specialists, and audiologists. Sinopulmonary involvement and hearing manifestations are very common in this population, and speech understanding in noise is often impaired. These manifestations impact QOL in various areas. A multidisciplinary and objective clinical assessment should be performed routinely, and appropriate treatment on a case-by-case basis may lead to a reduction in morbidity and improve QOL. Acknowledgements:None Funding:None

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Hosted file Tables Ped Pulm.docx available at https://authorea.com/users/365219/articles/1298344- evaluation-of-pulmonary-and-otological-manifestations-in-primary-ciliary-dyskinesia- and-their-effect-on-quality-of-life 10