Patients with diagnosed PCD and concordant outcome according to all three guidelines (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 (more details in supplementary table S1) | TEM BEAT-PCD classification [12] | Genetics ACMG-classification [27] | Costs¶¶ EUR | Outcome ATS | Outcome ERS | Outcome PCD-UNIBE | Main tools leading to diagnosis |
| 1 (264) | 5.0 | f | Chronic wet cough Recurrent serous otitis media Recurrent Haemophilus influenzae infections Less symptoms on antibiotics | 214¶ | Inconclusive | Suspicious for PCD | DNALI1 missing or strongly reduced (ALI) | IDA defect & tubular disorganisation >50% (ALI) class 1 defect, diagnostic for PCD | No likely pathogenic or pathogenic variant in 43 genes tested (2020), negative | 7855 | PCD diagnosed hallmark (class 1) TEM defect | PCD positive HSVM repeatedly suggestive hallmark (class 1) TEM defect | PCD positive HSVM suggestive class 1 TEM defect | Clinics TEM cell culture |
| 2 (290) | 17.4 | f | Recurrent rhinitis Rhinopolyps Recurrent infections with Haemophilus influenza Serous otitis media | 2 2 0.5 1.6 | High evidence for PCD | High evidence for PCD | DNAH11 repeatedly missing (ALI) | Non-diagnostic (ALI) | Monoallelic DNAH11 mutation, non-diagnostic, classified likely pathogenic (4) if biallelic | 6855 | PCD diagnosed suggestive clinics nNO repeatedly low | PCD highly likely nNO repeatedly low HSVM repeatedly suggestive | PCD highly likely nNO repeatedly low HSVM suggestive IF with DNAH11 missing | Clinics low nNO HSVM cell culture IF |
| 3 (284) | 15.0 | m | Situs inversus totalis Chronic rhinitis Chronic wet cough | 40 40 | High evidence for PCD | High evidence for PCD | DNAH11 missing (ALI) | Non-diagnostic (fresh & ALI) | Biallelic DNAH11 mutation, non-diagnostic, classified unknown significance (3) | 7855 | PCD diagnosed suggestive clinics nNO repeatedly low | PCD highly likely nNO repeatedly low HSVM repeatedly suggestive | PCD highly likely HSVM suggestive IF with DNAH11 missing | Clinics HSVM cell culture IF |
| 5 (266) | 15.0 | m | Serous otitis media Chronic rhinitis Recurrent low nNO | 21 6 10 9.5+ | High evidence for PCD | High evidence for PCD | DNAH11 missing (ALI) | Non-diagnostic (fresh & ALI) | Biallelic DNAH11 mutation, compound heterozygous, diagnostic, classified pathogenic (5) & likely pathogenic (4) | 7908 | PCD diagnosed suggestive clinics nNO repeatedly low genetics | PCD highly likely nNO repeatedly low HSVM repeatedly suggestive genetics | PCD highly likely HSVM suggestive IF with DNAH11 missing genetics | Clinics low nNO HSVM cell culture IF genetics |
| 6 (267) | 1.4 | m | Situs inversus totalis Chronic rhinitis | 4.5 ¶,+,§,f | Inconclusive | High evidence for PCD | DNAH11 missing (fresh) | Non-diagnostic | Biallelic DNAH11 mutation, diagnostic, classified pathogenic (5) | 5855 | PCD diagnosed (nNO low) confirmed genetics | PCD positive HSVM suggestive confirmed genetics | PCD positive HSVM suggestive IF with DNAH11 missing confirmed genetics | Clinics HSVM cell culture IF genetics |
| 7 (298) | 2.8 | m | Situs inversus totalis NRDS Nasal secretion Productive cough | 5 29.5¶,+ | PCD likely | Cell culture not successful | Inconclusive | - | Biallelic DNAH5 mutation, diagnostic, classified pathogenic (5) | 3925 | PCD diagnosed nNO repeatedlylow¶ confirmed genetics | PCD positive HSVM suggestive confirmed genetics | PCD positive HSVM suggestive confirmed genetics | Clinics genetics |
| 8 (318) | 16.9 | f | Situs inversus totalis Chronic wet cough | 205 163 | PCD likely | High evidence for PCD | DNAH11 missing (ALI) | - | Biallelic DNAH11 mutation, diagnostic, classified pathogenic (5) & likely pathogenic (4) | 4855 | PCD diagnosed suggestive clinics confirmed genetics | PCD positive suggestive clinics HSVM repeatedly suggestive confirmed genetics | PCD positive suggestive clinics HSVM pathological IF with DNAH11 missing confirmed genetics | Clinics IF cell culture genetics |
| 10 (338) | 14.1 | f | Chronic purulent cough Chronic rhinitis obstructive & restrictive ventilation disorder NRDS Positive family history (mother 11, brother 12) | 7+,§ | High evidence for PCD | High evidence for PCD | DNAH5 completely missing (fresh and ALI) | ODA & IDA missing >50% (ALI) class 1 defect, diagnostic for PCD | - | 2877 | PCD diagnosed nNO low hallmark (class 1) TEM defect | PCD positive nNO low HSVM repeatedly suggestive hallmark (class 1) TEM defect | PCD positive HSVM suggestive class 1 TEM defect IF with DNAH5 missing | HSVM cell culture IF TEM |
| 11 (339) | 42.4 | f | Chronic purulent cough Situs inversus totalis Bronchiectasis (mother of patients 10 & 12) | - | Inconclusive | High evidence for PCD | DNAH5 completely missing (fresh and ALI) | ODA & IDA missing >50% (ALI) class 1 defect, diagnostic for PCD | - | 2802 | PCD diagnosed hallmark (class 1) TEM defect | PCD positive HSVM repeatedly suggestive hallmark (class 1) TEM defect | PCD positive HSVM suggestive class 1 TEM defect IF with DNAH5 missing | HSVM cell culture IF TEM |
| 12 (354) | 9.6 | m | Chronic purulent cough Chronic rhinitis Positive family history (mother 11, sister 10) | 7+,§ | High evidence for PCD | Cell culture not successful | Inconclusive | ODA & IDA missing >50% (fresh) class 1 defect, diagnostic for PCD | - | 2925 | PCD diagnosed nNO low hallmark (class 1) TEM defect | PCD positive nNO low HSVM repeatedly suggestive hallmark (class 1) TEM defect | PCD positive HSVM suggestive class 1 TEM defect | HSVM TEM |
| 13 (343) | 17.4 | m | Chronic wet cough Chronic rhinitis and nasal obstruction Positive family history | 5 9 2+ | PCD likely | PCD likely | All proteins present## | - | Biallelic HYDIN mutation, diagnostic, classified pathogenic (5) | 4855 | PCD diagnosed nNO repeatedly low confirmed genetics | PCD positive nNO low HSVM repeatedly suggestive confirmed genetics | PCD positive nNO low HSVM suggestive confirmed genetics | Clinics nNO genetics |
| 20 (346) | 66.0 | f | Situs inversus totalis Positive family history (sister of 21, 22 & 23) Chronic rhinitis Chronic wet cough Nasal polyposis Recurrent sinusitis Bronchiectasis Shortness of breath | 9+,§ | High evidence for PCD | High evidence for PCD | DNAH11 missing (ALI) | Non-diagnostic | Biallelic DNAH11 mutation, diagnostic, classified likely pathogenic (4) | 5855 | PCD diagnosed suggestive clinics nNO low confirmed genetics | PCD positive nNO low HSVM repeatedly suggestive confirmed genetics | PCD positive nNO low HSVM suggestive IF with DNAH11 missing confirmed genetics | HSVM cell culture IF genetics |
| 21 (347) | 65.0 | f | Positive family history (sister of 20, 22 & 23) Chronic rhinitis Chronic cough Subfertility | 9+,§ | High evidence for PCD | High evidence for PCD | DNAH11 missing (ALI) | Non-diagnostic (ALI) | Biallelic DNAH11 mutation, diagnostic, classified likely pathogenic (4) | 5855 | PCD diagnosed suggestive clinics nNO low confirmed genetics | PCD positive nNO low HSVM repeatedly suggestive confirmed genetics | PCD positive nNO low HSVM suggestive IF with DNAH11 missing confirmed genetics | HSVM cell culture IF genetics |
| 22 (348) | 67.8 | m | Positive family history (sister of 20, 21 & 23) Chronic wet cough Nasal polyposis Chronic rhinitis | 1+,§ | High evidence for PCD | High evidence for PCD | DNAH11 missing (ALI) | Non-diagnostic (ALI) | Biallelic DNAH11 mutation, diagnostic, classified likely pathogenic (4) | 5855 | PCD diagnosed suggestive clinics nNO low confirmed genetics | PCD positive nNO low HSVM repeatedly suggestive confirmed genetics | PCD positive nNO low HSVM suggestive IF with DNAH11 missing confirmed genetics | HSVM cell culture IF genetics |
| 23 (349) | 68.9 | f | Positive family history (sister of 20, 21 & 22) Chronic rhinitis Chronic wet cough | 5.5+,§ | High evidence for PCD | High evidence for PCD | DNAH11 missing (ALI) | Non-diagnostic (ALI) | Biallelic DNAH11 mutation, diagnostic, classified likely pathogenic (4) | 5855 | PCD diagnosed suggestive clinics nNO low confirmed genetics | PCD positive nNO low HSVM repeatedly suggestive confirmed genetics | PCD positive nNO low HSVM suggestive IF with DNAH11 missing confirmed genetics | HSVM cell culture IF genetics |
| 24 (359) | 0.1 | f | Situs inversus totalis NRDS Chronic nasal secretion Chronic productive cough | <1+,§,□ | High evidence for PCD | High evidence for PCD | DNAH5, DNAH9, DNAH11, DNAI1, DNAI2 missing (ALI) | - | Not yet performed, brother with diagnostic, biallelic DNAH5-mutation | 2014 | PCD diagnosed suggestive clinics (nNO low) genetics unclear (brother with confirmed mutation) | PCD highly likely HSVM suggestive | PCD highly likely HSVM suggestive IF with proteins missing | HSVM cell culture IF (genetics) |
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]. ¶: child <5 years old. +: cystic fibrosis not excluded by sweat test or genetic testing. §: single nNO measurement. f: nNO measurement during rhinitis. ##: DNAH5, GAS8, RSPH9 and DNAH11 stained. ¶¶: 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.