Retrospective examination of clinical and laboratory data at the diagnosis and follow-up of primary ciliary dyskinesia patients

Primary ciliary dyskinesia (PCD) is a genetic disease that results from disorders in the structure and/or functions of cilia, which leads to the impairment of mucociliary transport and is mostly inherited in an autosomal recessive manner. Ciliary dysfunction causes functional disorders in many organs where cilia perform their duties, especially in the respiratory system. In this study, the clinical characteristics and genetic mutations of PCD patients in our country were examined by sharing the experience of a multidisciplinary single center. A total of 361 patients, who were followed up with a diagnosis of PCD between January 1, 1990, and December 31, 2022, at the Hacettepe University Faculty of Medicine Department of Pediatric Pulmonology were retrospectively evaluated from among 145 patients who came to our center for follow-up at least once after 2017. Of the patients in the study group, 66 were female (45.5%) and 79 were males (54.5%). The mean age of the included patients was 15.91±6.26 years, and the median age was 16.2 years. The mean age at diagnosis of the patients was 7.4 years, and the median age was 7.3 years. A statistically significant relationship was found between the age at diagnosis and the history of respiratory distres syndrome (RDS) in the neonatal period (p=0.014), the presence of situs inversus totalis (p=0.001), the history of newborn intensive care unti (NICU) admission (p=0.000), and the presence of congenital heart disease (p=0.006). The age at diagnosis was lower in those with a history of RDS in the neonatal period (6.75 years), situs inversus totalis (4.43 years), NICU admission (6.58 years), and congenital heart disease (5.29 years). A negative moderate correlation was found between the PICADAR score and the age at diagnosis (p:0.000, r=-0.50). There is a statistically significant positive correlation between hearing loss and a history of recurrent otitis media (p=0.000). The rate of hearing loss is higher in those with recurrent otitis media. In the diagnosis of patients, in addition to clinical findings, nasal nitric oxide (nNO) measurement (75), high speed videomicroscopy (HSVM) (142), transmission electron microscopy (TEM) (3), and genetic analysis (52) results were evaluated. One pathogenic variant was detected in 8 of the patients who underwent genetic analysis. Therefore, 47 of the patients included in the study were considered definitive PCD, and 98 were considered possible PCD. The most commonly seen homozygous mutations were; DNAH5 homozygous (26 alleles), CCDC40 homozygous (8 alleles) and CCNO homozygous (6 alleles) mutations, respectively. The identified mutations have been classified based on the localization of the proteins reported to be affected in the literature: 1) Outer dynein arm (ODA): DNAH5, ODAD1, DNAH11, ARMC4, DNAL1, DNAI1, and DNAI2; 2) Nexin-Dynein regulatory complex: CCDC40, CCDC39, DRC1; 3) Cytoplasmic protein: CCNO, DNAAF2, ZMYND10, DNAAF4, DNAH8, DNAH10; 4) Radial spoke: RSPH4A, RSPH3; 5) Central complex: HYDIN. None of the patients with defects in radial spoke or central complex have been found to have situs inversus totalis. Respiratory function test values were found to be lower in those with CCNO homozygous and RSPH3 homozygous mutations compared to other mutations. The most commonly seen findings in lung X-rays taken at the time of diagnosis are; peribronchial thickening (71.7%), atelectasis (62%), and bronchiectasis (40.3%) respectively. In the lung imaging of patients in their last check-ups (X-ray, CT), the most frequently observed site of atelectasis was the right middle lobe (46.7%), and its size was found to be subsegmental (65.6%). A weak positive correlation was found between the average body mass index (BMI) z scores and mean FEV1 (%) values measured in 2017 and the last check-up (r=0.30 and r=0.39). Patients with high BMI z scores had higher FEV1 (%) values. When the sputum culture results from the last 6 months were examined, it was observed that Haemophilius influenzae (H. influenzae) was present in 47 (35.3%) patients, Candida spp. in 25 (18.8%) patients, methicillin sensitive staphylococccus aereus (MSSA) in 14 (10.5%) patients, and Pseudomonas aeruginosa (P. aeruginosa) in 12 (9%) patients. The most common causes of colonization were found to be H. influenzae (30) and P. aeruginosa (9). There was a statistically significant relationship between the presence of chronic colonization and pneumoniae in the last 6 months (p=0.012). Sixty one (42.1%) patients were recorded to have regular chest physiotherapy. Postural drainage and percussion, the most commonly applied chest physiotherapy method, was preferred by 81 (55.9%) patients. Lobectomy was performed on 13 (9%) patients. Three of these patients (23%) were referred to our center after the lobectomy. Spirometric evaluations of patients who underwent lobectomy yielded statistically significant results when compared to those who did not. FEV1 (%), FEV1 z scores, FVC (%), and FVC z scores were lower in patients who underwent lobectomy compared to those who did not. In our country, where consanguineous marriages are common, increasing awareness of PCD among physicians, expanding the use of diagnostic methods across centers, increasing the accessibility of multidisciplinary teams, and ensuring regular follow-up of patients may have a positive effect on the treatment of the disease.