BackgroundThe lung clearance index (LCI) derived from the multiple breath inert gas washout (MBW) test reflects global ventilation distribution inhomogeneity. It is more sensitive than forced expiratory volume in 1 s (FEV 1 ) for detecting abnormal airway function and correlates closely with structural lung damage in children with cystic fibrosis, which shares features with primary ciliary dyskinesia (PCD). Normalised phase III slope indices S cond and S acin reflect function of the small conducting and acinar airways, respectively. The involvement of the peripheral airways assessed by MBW tests has not been previously described in PCD. Methods A cross-sectional MBW study was performed in 27 children and adolescents with verified PCD, all clinically stable and able to perform lung function tests. LCI, S cond (n¼23) and S acin (n¼23) were derived from MBW using a mass spectrometer and sulfur hexafluoride as inert marker gas. MBW indices were compared with present age, age at diagnosis and spirometry findings, and were related to published normative values. Results LCI, S cond and S acin were abnormal in 85%, 96% and 78% of patients with PCD and in 81%, 93% and 79%, respectively, of 13/27 subjects with normal FEV 1 . LCI and S acin correlated significantly while S cond did not correlate with any other lung function parameters. None of the lung function measurements correlated with age or age at diagnosis. Conclusions PCD is characterised by marked peripheral airway dysfunction. MBW seems promising in the early detection of lung damage, even in young patients with PCD. The relationship of MBW indices to the outcome of long-term disease and their role in the management of PCD need to be assessed.

BackgroundAlthough aerobic fitness is regarded as an overall prognostic measure of morbidity and mortality, its evaluation in the chronic progressive sinopulmonary disease primary ciliary dyskinesia (PCD) has been infrequently and inconsistently reported. Here we assessed peak oxygen uptake (VO2peak) in a large well-characterized cohort of PCD patients, and explored whether VO2peak was associated with parameters of pulmonary function, self-reported physical limitations, and physical activity level.MethodsVO2peak, spirometry, diffusing capacity, whole-body plethysmography, and nitrogen multiple breath inert gas washout (N2 MBW) were assessed in a cross-sectional, single-occasion study of clinically stable children and young adults with PCD. We used a questionnaire including self-reported physical limitations in everyday life or in vigorous activities, and estimation of weekly hours of strenuous physical activity. VO2peak in PCD patients was compared with that in matched, healthy control subjects and a national reference.ResultsForty-four PCD patients aged 6–29 years exhibited reduced VO2peak compared to healthy controls (P<0.001) and the national reference. VO2peak was abnormal (z-score <–1.96) in 34% of PCD patients. Spirometric values, RV/TLC, and indices of N2 MBW were significantly abnormal, but VO2peak only correlated with FEV1 and DLCO/VA. VO2peak correlated with complaints of moderate or significant limitations in vigorous activities (P = 0.0001), exhibited by 39% of PCD patients.ConclusionOne-third of PCD patients exhibited substantially lower aerobic fitness than healthy subjects. Aerobic fitness correlated with FEV1, DLCO/VA and self-reported complaints of limitations in vigorous physical activity. These findings are most likely explained by PCD pulmonary disease and its impact on pulmonary function and physical ability. Considering fitness as an important outcome and including regular strenuous physical activity in PCD treatment would probably altogether increase pulmonary clearance, lung function, aerobic fitness, and quality of life, and prevent lifestyle-related diseases.

Cn@TO6 may be suggested as a potential test-shortening endpoint in school children with PCD. In CF, early test termination may reduce measurement power with advancing pulmonary disease, suggesting differences in underlying pathophysiology. Two technically acceptable N2 MBW runs may be sufficient in school children irrespective of diagnosis with CF or PCD. Pediatr Pulmonol. 2016;51:624-632. © 2015 Wiley Periodicals, Inc.

The feasibility of measuring FeNO was highly age-dependent and not applicable in children under age 4. NMBW was feasible in the majority of preschool children. S, but not FeNO, could discriminate between children with asthma and healthy controls.

In children with comparable CF lung disease, spirometric breath hold monitoring during examination yielded a large difference in lung volume between inhalation and exhalation, and allowed for a significantly greater measured change in lung density and TA score, compared to unmonitored breath hold maneuvers. This has implications to the clinical use of chest CT, especially in children with early CF lung disease.

This is the first report indicating that cardiopulmonary fitness is equally and consistently reduced in both children with PCD and CF along with a consistent lower pulmonary function in PCD compared with CF. A certain reservation for possible selection bias and the small number of patients is necessary. However, increased focus on early diagnosis, evidence-based treatment regimens and close clinical monitoring in PCD are warranted.

We report between-session variability of LCI using NMBW in school-age children and adolescents with CF. LCI changes exceeding 25% may be considered clinically relevant. TestPoint® and Spiroware® can be used interchangeably in longitudinal studies.

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