Figures
- FIGURE 1
a) Diagnostic breakdown of our cohort. b) Lobar distribution of bronchiectasis seen in adult primary ciliary dyskinesia. c) Cumulative respiratory microbial colonisation in our cohort. H. influenzae: Haemophilus influenzae; S. pneumoniae: Streptococcus pneumoniae; S. aureus: Staphylococcus aureus; MRSA: methicillin-resistant S. aureus; P. aeruginosa: Pseudomonas aeruginosa; M. catarrhalis: Moraxella catarrhalis; A. fumigatus: Aspergillus fumigatus; NTM: nontuberculous mycobacteria.
- FIGURE 2
a) Correlation between age at diagnosis and baseline forced expiratory volume in 1 s (FEV1) (r= −0.30, p=0.01) in our adult primary ciliary dyskinesia cohort. b) Increased age at diagnosis was seen for those with Pseudomonas aeruginosa colonisation compared with those without (difference in medians 17 years (95% CI 4.5–20 years); p=0.002). c) Significantly impaired FEV1 at baseline was also seen in those with P. aeruginosa colonisation (difference in medians −8.5% pred (95% CI −17– −1.0% pred); p=0.02). Horizontal lines and whiskers represent the mean and sem, respectively.
- FIGURE 3
Predicted longitudinal forced expiratory volume in 1 s (FEV1) for individual patients estimated from mixed models. Models allowed for a random effect on age. a) Mixed model of the cohort adjusted for ciliary ultrastructure and age. b) Mixed model adjusting for ciliary ultrastructure and stratified by high-resolution computed tomography (HRCT) score of severity of bronchial wall dilatation. c) Mixed model adjusting for ciliary ultrastructure and stratified by HRCT score of extent of bronchiectasis. d) Mixed model stratified by ciliary ultrastructure. a–d) Predicted longitudinal FEV1 values are shown, rather than observed FEV1 values; therefore, the points follow a strict linear trend. e) Estimated projected decline calculated from mixed models within the three categories of HRCT severity of bronchial wall dilatation (using an 18-year-old with 100% predicted FEV1 as a starting point).
Tables
- TABLE 1
General characteristics of adult primary ciliary dyskinesia patients
Total patients 151 Age in 2014 years 35 (19–75; 26–47) Male n (%) 58 (38.4) Age at diagnosis years 23.5 (<1–72; 10–36) Smokers n (%) 12 (8.0) Length of follow-up years 7 (1–34; 3–13) All-cause mortality n (%) 7 (4.6) Respiratory cause mortality n (%) 5 (3.3) Nasal nitric oxide Patients analysed 97 ppb 42.0 (5.0–229.0; 23.0–70.0) nL·min−1 10.5 (1.3–57.3; 5.8–17.5) Ciliary beat frequency Patients analysed 144 Hz 0 (0–16.85)# ≥8 Hz % 80.7 >8 Hz % 19.3 Ciliary TEM ultrastructure n (%) Patients analysed 141 Inner and outer dynein arm defect 36 (25.5) Outer dynein arm defect 56 (39.7) Inner dynein arm defect 3 (2.1) Inner dynein arm defect with microtubular disorganisation 14 (9.9) Central pair and transposition defect 13 (9.2) Normal ciliary ultrastructure 16 (11.3) Inconclusive 3 (2.1) Ciliary TEM ultrastructure groups n (%) Patients analysed 138 Outer arm±inner arm defect 92 (66.7) Microtubular defects 27 (19.6) Normal/inconclusive 19 (13.8) Situs inversus n (%) Patients analysed 144 With situs inversus 55 (38.2) Inner and outer dynein arm defect 16 (29.1) Outer dynein arm defect 27 (49.1) Inner dynein arm defect 1 (1.8) Inner dynein arm defect with microtubular disorganisation 4 (7.3) Central pair and transposition defect 0 (0) Normal ciliary ultrastructure 3 (5.5) Unavailable 4 (7.3) HRCT scoring Patients analysed 93 Extent of bronchiectasis % 44.4 (0–100.0; 33.3–63.9) Severity of bronchial wall dilatation % 50.0 (0.0–83.3; 33.3–66.7) Bronchial wall thickness % 33.3 (5.6–83.3; 22.2–44.4) Small airway mucus plugging % 58.3 (0.0–100.0; 41.7–75.0) Large airway mucus plugging % 0.0 (0.0–58.3; 0.0–0.0) Mosaicism % 61.2 (0.0–85.0; 47.5–71.7) Emphysema % 0.0 (0.0–0.0)# Pulmonary function at baseline Patients analysed 118 FEV1 % pred 71.5±21.5 FEV1/FVC % 69.7±14.7 TLC % pred 104.6±16.8 RV/TLC % 140.1±33.2 TLCO % pred 82.7±18.6 KCO % pred 96.8±14.1 Cumulative sputum microbiology during follow-up period n (%) Pseudomonas aeruginosa colonisation 68 (44.4) NTM infection 5 (3.3) Allergic bronchopulmonary aspergillosis 4 (2.6) Lung function change with age Patients analysed 82 Estimated change in FEV1 % pred per year −0.49 (−1.68–0.70)¶ Estimated change after adjusting for age and sex mL·year−1 −27.34 (−65.13–10.44)¶ Data are presented as median (range; interquartile range) or mean±sd, unless otherwise stated. TEM: transmission electron microscopy; HRCT: high-resolution computed tomography; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; TLC: total lung capacity; RV: residual volume; TLCO: transfer factor of the lung for carbon monoxide; KCO: transfer coefficient of the lung for carbon monoxide, i.e. gas transfer ability per unit volume of lung; NTM: nontuberculous mycobacteria. #: median (range); ¶: based on regression coefficient (estimated range where 95% of values would lie); see main text for details.
- TABLE 2
Analysis of association between covariates and repeated measurements of forced expiratory volume in 1 s % predicted, from multilevel models
Covariate B coefficient
(95% CI)#p-value p-value from likelihood ratio test for interaction with age¶ Patients included in analysis+ Sex 4.02 (−4.02–12.05) 0.33 108 BMI 0.31 (−0.17–0.79) 0.21 108 Age at diagnosis 0.001 (−0.35–0.35) 1.00 59 Nasal nitric oxide 0.10 (−0.01–0.22) 0.09 68 Ciliary beat frequency 6.47 (−15.76–2.82) 0.17 101 Pseudomonas aeruginosa −0.37 (−2.37–1.63) 0.72 107 Ciliary ultrastructure by TEM 0.03§ 0.04 97 Normal or inconclusive 0.00 Outer±inner arm defect 3.90 (−7.01–14.80) Microtubular defects 10.29 (−23.59–3.01) Extent of bronchiectasis −0.18 (−0.41–0.05)ƒ 0.122 0.03 68 Severity of bronchial wall dilatation −0.17 (−0.36–0.02)ƒ 0.08 0.01+ 68 Bronchial wall thickness −0.29 (−0.56– −0.01)ƒ 0.045 0.06+ 68 Small airway plugging (continuous) −0.29 (−0.46– −0.13)ƒ <0.001 0.196+ 68 Large airway plugging −0.63 (−1.08– −0.17)ƒ 0.007 0.19+ 68 Mosaicism −0.26 (−0.46– −0.07)ƒ 0.008 0.16+ 68 BMI: body mass index; TEM: transmission electron microscopy. #: B coefficients are to be interpreted as the change in forced expiratory volume in 1 s (FEV1) for each unit change of the covariate after adjusting for age at which the measurement was made; ¶: tests for interaction with age assess whether these covariates affect how FEV1 changes as patients get older; +: patients included in each of these regression analyses had non-missing data for FEV1, age at the time the FEV1 measure was taken, the covariate under study, and ciliary ultrastructure where this was adjusted for; §: the p-value for this covariate relates to the covariate as a whole rather than one level or another; ƒ: after additionally adjusting for ciliary ultrastructure.
- TABLE 3
Mean change in forced expiratory volume in 1 s (FEV1) % predicted per year in different patient subgroups, estimated from multilevel models
Patient subgroups Mean change in FEV1 % pred per year Range for 95% of patients' changes in FEV1 % pred Patients in model# Ciliary ultrastructure by TEM¶ Microtubular defects −0.75 −2.08–0.58 18 Outer±inner arm defect −0.51 −1.41–0.39 64 Normal or inconclusive −0.13 −1.53–1.28 15 Extent of bronchiectasis+ <44% −0.08 −0.92–0.75 20 ≥44% and <55% −0.65 −1.52–0.22 25 ≥55% −0.59 −2.13–0.95 23 Severity of bronchial wall dilatation+ <33% 0.16 −0.20–0.53 12 ≥33% and <67% −0.57 −1.31–0.17 42 ≥67% −0.89 −2.74–0.95 14 TEM: transmission electron microscopy. #: models were run for different patient subgroups depending on their ciliary ultrastructure, extent of bronchiectasis and severity of bronchial wall dilatation; as well as this, patients were required to have non-missing data for FEV1, age at the time the FEV1 measure was taken and any other variables in the model. ¶: model stratified by ciliary ultrastructure by TEM categories. +: models stratified by high-resolution computed tomography categories where there was evidence of interaction with age (p<0.05); all adjusted for ciliary ultrastructure by TEM.
Supplementary material
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- Supplementary material - Supplementary methods and results
