Patients with discordant outcome (more details in supplementary table S1)
| Patient number (lab ID) | Age at referral years | Sex | Clinical features | nNO nL·min-1# | HSVM fresh (more details in supplementary table S1) | HSVM ALI (more details in supplementary table S1) | IF | TEM BEAT-PCD-TEM [12] classification | Genetics ACMG-classification [27] | Costsf EUR | Outcome ATS | Outcome ERS | Outcome PCD-UNIBE | Main tools leading to diagnosis |
| 4 (272) | 6.6 | M | Bronchiectasis Chronic wet cough Sister with similar symptoms | 175 | No evidence for PCD | No evidence for PCD | DNAH9 missing (ALI) | ODA & IDA Defect <50% (ALI) class 2 defect, PCD likely | Two DNAH9 variants in-cis, non-diagnostic | 5908 | PCD not diagnosed nNO normal Genetics non-diagnostic No hallmark TEM defect | PCD highly unlikely No hallmark TEM defect Genetics of unknown significance | PCD highly likely Class 2 TEM defect IF with DNAH9 missing | Clinics TEM cell culture IF |
| 9 (323) | 65.1 | M | Bronchiectasis Chronic wet cough Recurrent respiratory tract infections | 14¶ | High evidence for PCD | Inconclusive | DNAH9 repeatedly completely missing (ALI) | Non-diagnostic | No likely pathogenic or pathogenic variant found in 42 genes tested (2020) | 6908 | PCD diagnosed Suggestive clinics nNO low (single measurement) | PCD highly unlikely nNO low HSVM inconclusive TEM non-diagnostic Genetics negative | PCD highly likely nNO low HSVM inconclusive IF with DNAH9 missing | nNO cell culture IF |
| 14 (361) | 23.6 | F | Chronic productive cough Chronic rhinitis | 152 | Inconclusive | High evidence for PCD | All proteins present | Non-diagnostic (fresh) | Refused by patient | 3855 | PCD not diagnosed nNO normal TEM non-diagnostic (genetics to be done) | PCD highly likely HSVM repeatedly suggestive | PCD highly likely HSVM suggestive | HSVM cell culture |
| 15 (253) | 9.2 | m | PICADAR 6 chronic wet cough Chronic rhinitis Cardiac malformation (pulmonary & tricuspid atresia) Recurrent otitis media Immune deficiency | 20 9+ | No evidence for PCD | No evidence for PCD | All proteins present | - | - | 1908 | PCD diagnosed Suggestive clinics nNO repeatedly low | PCD highly unlikely HSVM fresh & ALI normal | PCD highly unlikely HSVM fresh & ALI normal IF without protein missing | nNO |
| 16 (285) | 15.6 | m | Chronic purulent cough Chronic rhinitis Premature birth Obstructive sleep apnoea | 7.5§ 7 | PCD likely | No evidence for PCD | DNAH9 inconclusive (ALI) inconclusive | Non-diagnostic (ALI) | No likely pathogenic or pathogenic variant found in 43 genes tested (2020) | 6249 | PCD diagnosed Suggestive clinics nNO repeatedly low | PCD highly unlikely HSVM ALI normal TEM non-diagnostic Genetics negative | PCD highly unlikely HSVM ALI normal TEM non-diagnostic Genetics negative | nNO |
| 17 (294) | 5.0 | f | Chronic wet cough Recurrent respiratory tract infections Bronchiectasis | 11 12 | No evidence for PCD | No evidence for PCD | No evidence for PCD | - | No likely pathogenic or pathogenic variant found in 41 genes tested (2019) | 4930 | PCD diagnosed Suggestive clinics nNO repeatedly low | PCD highly unlikely HSVM normal Genetics negative | PCD highly unlikely HSVM normal IF without protein missing Genetics negative | nNO |
| 18 (295) | 5.1 | f | Chronic cough Recurrent respiratory tract infections Recurrent otitis media | 5¶ | Inconclusive | No evidence for PCD | All proteins present | - | - | 1877 | PCD diagnosed Suggestive clinics nNO low (single measurement) | PCD highly unlikely HSVM normal | PCD highly unlikely HSVM normal IF without protein missing | nNO |
| 19 (319) | 6.5 | m | Premature birth NRDS & intensive care admittance Chronic rhinitis Chronic cough Recurrent bronchitis Bronchopulmonary dysplasia OSAS | 6.5§ 41 | No evidence for PCD | Inconclusive | No evidence for PCD | Non-diagnostic (ALI) | No likely pathogenic or pathogenic variant associated with PCD found in 6688 genes tested (2020) | 5855 | PCD diagnosed Suggestive clinics nNO repeatedly low | PCD highly unlikely HSVM normal TEM non-diagnostic | PCD highly unlikely HSVM normal TEM non-diagnostic IF without protein missing | nNO |
Single discordant outcome highlighted in italic letters. Bold text indicates results leading to a diagnosis of PCD and the final diagnosis. ACMG: American College of Medical Genetics and Genomics; ALI: air–liquid interface; ATS: American Thoracic Society; Array-CGH: array-based comparative genomic hybridisation; ERS: European Respiratory Society; f: female; HSVM: high-speed videomicroscopy; IDA: inner dynein arm; IF: immunofluorescence labelling; m: male; nNO: nasal nitric oxide; NRDS: neonatal respiratory distress syndrome; ODA: outer dynein arm; PCD: primary ciliary dyskinesia; PCD-UNIBE: comprehensive diagnostic centre at the University Children's Hospital, Inselspital Bern, Switzerland; TEM: transmission electron microscopy. #: these are mean values for nNO for the right and left side. The unit for nNO results at our centre is parts per billion (ppb). To obtain values in nL·min-1 the formula (ppb) × sampling flow rate (0.33 mL·min-1 for Ecomedics Analyzer CLD 88 sp) was used as proposed in Leigh et al. [18]. ¶: single nNO measurement. +: cystic fibrosis not excluded by sweat test or genetic testing. §: nNO measurement during rhinitis. f: remark about the costs: the costs were estimated based on costs that are billed for each method performed (for costs of each method see supplementary table S2 and figure S1). The costs may be higher than in other studies; however, we have to consider that prices and salaries are usually higher in Switzerland compared to other countries.