TTC12 Loss-of-Function Mutations Cause Primary Ciliary Dyskinesia and Unveil Distinct Dynein Assembly Mechanisms in Motile Cilia Versus Flagella.

Cilia and flagella are evolutionarily conserved organelles whose motility relies on the outer and inner dynein arm complexes (ODAs and IDAs). Defects in ODAs and IDAs result in primary ciliary dyskinesia (PCD), a disease characterized by recurrent airway infections and male infertility. PCD mutations in assembly factors have been shown to cause a combined ODA-IDA defect, affecting both cilia and flagella. We identified four loss-of-function mutations in TTC12, which encodes a cytoplasmic protein, in four independent families in which affected individuals displayed a peculiar PCD phenotype characterized by the absence of ODAs and IDAs in sperm flagella, contrasting with the absence of only IDAs in respiratory cilia. Analyses of both primary cells from individuals carrying TTC12 mutations and human differentiated airway cells invalidated for TTC12 by a CRISPR-Cas9 approach revealed an IDA defect restricted to a subset of single-headed IDAs that are different in flagella and cilia, whereas TTC12 depletion in the ciliate Paramecium tetraurelia recapitulated the sperm phenotype. Overall, our study, which identifies TTC12 as a gene involved in PCD, unveils distinct dynein assembly mechanisms in human motile cilia versus flagella.

Nasal nitric oxide measurement in children for the diagnosis of primary ciliary dyskinesia: European Respiratory Society technical standard.

Nasal nitric oxide (nNO) is extremely low in most people with primary ciliary dyskinesia (PCD) and its measurement is an important contributor to making the diagnosis. Existing guidelines and technical standards focus on nNO measurements in older, cooperative children using chemiluminescence analysers. However, measurements of nNO in pre-school-age children (age 2-5 years) may facilitate early diagnosis and electrochemical rather than chemiluminescence analysers are widely used. Pre-schoolers often need different methods to be employed when measuring nNO. Hence, a European Respiratory Society Task Force has developed this technical standard as the first step towards standardising sampling, analysis and reporting of nNO measured as part of the diagnostic testing for PCD in all age groups, including pre-school-age children. Furthermore, we considered both chemiluminescence and electrochemical analysers that are in use worldwide. There was a paucity of quality evidence for electrochemical analysers and sampling methods used in young children, and the Task Force proposes future research priorities to allow updates of this technical standard.

Longitudinal assessment of loss and gain of lung function in childhood asthma.

OBJECTIVE: The Childhood Asthma Management Program revealed that 25.7% of children with mild to moderate asthma exhibit loss of lung function. The objective was to assess the trajectories of function by means of serial FEV1 in asthmatic children participating in out-of-hospital follow-up. METHODS: A total of 295 children (199 boys) who had undergone at least 10 spirometry tests from the age of 8 were selected from a single-center open cohort. The annualized rate of change (slope) for prebronchodilator FEV1 (percent predicted) was estimated for each participant and three patterns were defined: significantly positive slope, significantly negative slope, and null slope (non-significant P-value; Pearson test). The standard deviation (SD) of each individual slope was recorded as a variability criterion of FEV1. RESULTS: The median (25th; 75th percentile) age at inclusion and the last visit was 8.5 (8.2; 9.3) and 15.4 (14.8, 16.0) years, respectively. Tracking of function (null slope) was observed in 68.8% of the children, while 27.8% showed a loss of function or reduced growth (negative slope) and 3.4% showed a gain in function (positive slope). The children characterized by loss of function depicted a better initial function and a lower FEV1 variability during their follow-up than children with tracking or gain of lung function. At the last visit, these children were characterized by a lower lung function than children with tracking or gain of lung function. CONCLUSION: Better initial FEV1 value and less FEV1 variability are associated with loss of lung function or reduced lung growth in asthmatic children.

Digital Action Plan (Web App) for Managing Asthma Exacerbations: Randomized Controlled Trial.

BACKGROUND: A written action plan (WAP) for managing asthma exacerbations is recommended. OBJECTIVE: We aimed to compare the effect on unscheduled medical contacts (UMCs) of a digital action plan (DAP) accessed via a smartphone web app combined with a WAP on paper versus that of the same WAP alone. METHODS: This randomized, unblinded, multicenter (offline recruitment in private offices and public hospitals), and parallel-group trial included children (aged 6-12 years) or adults (aged 18-60 years) with asthma who had experienced at least 1 severe exacerbation in the previous year. They were randomized to a WAP or DAP+WAP group in a 1:1 ratio. The DAP (fully automated) provided treatment advice according to the severity and previous pharmacotherapy of the exacerbation. The DAP was an algorithm that recorded 3 to 9 clinical descriptors. In the app, the participant first assessed the severity of their current symptoms on a 10-point scale and then entered the symptom descriptors. Before the trial, the wordings and ordering of these descriptors were validated by 50 parents of children with asthma and 50 adults with asthma; the app was not modified during the trial. Participants were interviewed at 3, 6, 9, and 12 months to record exacerbations, UMCs, and WAP and DAP use, including the subjective evaluation (availability and usefulness) of the action plans, by a research nurse. RESULTS: Overall, 280 participants were randomized, of whom 33 (11.8%) were excluded because of the absence of follow-up data after randomization, leaving 247 (88.2%) participants (children: n=93, 37.7%; adults: n=154, 62.3%). The WAP group had 49.8% (123/247) of participants (children: n=45, 36.6%; mean age 8.3, SD 2.0 years; adults: n=78, 63.4%; mean age 36.3, SD 12.7 years), and the DAP+WAP group had 50.2% (124/247) of participants (children: n=48, 38.7%; mean age 9.0, SD 1.9 years; adults: n=76, 61.3%; mean age 34.5, SD 11.3 years). Overall, the annual severe exacerbation rate was 0.53 and not different between the 2 groups of participants. The mean number of UMCs per year was 0.31 (SD 0.62) in the WAP group and 0.37 (SD 0.82) in the DAP+WAP group (mean difference 0.06, 95% CI -0.12 to 0.24; P=.82). Use per patient with at least 1 moderate or severe exacerbation was higher for the WAP (33/65, 51% vs 15/63, 24% for the DAP; P=.002). Thus, participants were more likely to use the WAP than the DAP despite the nonsignificant difference between the action plans in the subjective evaluation. Median symptom severity of the self-evaluated exacerbation was 4 out of 10 and not significantly different from the symptom severity assessed by the app. CONCLUSIONS: The DAP was used less often than the WAP and did not decrease the number of UMCs compared with the WAP alone. TRIAL REGISTRATION: ClinicalTrials.gov NCT02869958; https://clinicaltrials.gov/ct2/show/NCT02869958.

Association between lung function of school age children and short-term exposure to air pollution and pollen: the PARIS cohort.

BACKGROUND: Daily levels of ambient air pollution and pollen may affect lung function but have rarely been studied together. We investigated short-term exposure to pollen and air pollution in relation to lung function in school-age children from a French population-based birth cohort. METHODS: This study included 1063 children from the PARIS (Pollution and Asthma Risk: an Infant Study) cohort whose lung function and FeNO measurements were performed at age 8 years old. Exposure data were collected up to 4 days before testing. We estimated daily total pollen concentration, daily allergenic risk indices for nine pollen taxa, as well as daily concentrations of three air pollutants (particulate matter less than 10 µm (PM10), nitrogen dioxide (NO2), ozone (O3)). Children with similar pollen and air pollution exposure were grouped using multidimensional longitudinal cluster analysis. Associations between clusters of pollen and air pollution exposure and respiratory indices (FEV1, FVC, FeNO) were studied using multivariable linear and logistic regression models adjusted for potential confounders. RESULTS: Four clusters of exposure were identified: no pollen and low air pollution (Cluster 1), grass pollen (Cluster 2), PM10 (Cluster 3) and birch/plane-tree pollen with high total pollen count (Cluster 4). Compared with children in Cluster 1, children in Cluster 2 had significantly lower FEV1 and FVC levels, and children from Cluster 3 had higher FeNO levels. For FEV1 and FVC, the associations appeared stronger in children with current asthma. Additional analysis suggested a joint effect of grass pollen and air pollution on lung function. CONCLUSION: Daily ambient chemical and biological air quality could adversely influence lung function in children.

Infant feeding clusters are associated with respiratory health and allergy at school age in the PARIS birth cohort.

BACKGROUND: As infant feeding may influence allergy development, we aimed to identify groups of infants based on feeding practices and to examine their associations with respiratory health/allergy at 8 years in the PARIS birth cohort. METHODS: Data on breastfeeding, consumption of infant formula (regular, pre-/probiotics, partially hydrolysed with hypoallergenic label [pHF-HA], extensively hydrolysed [eHF], soya) and solid food introduction were collected using repeated questionnaires at 1, 3, 6, 9 and 12 months. Infants with similar feeding practices over the first year of life were grouped using multidimensional longitudinal cluster analysis. Respiratory/allergic morbidity was studied at 8 years as symptoms, doctor's diagnoses (asthma, hay fever, eczema, food allergy), and measurement of lung function, FeNO and specific IgE. Associations between feeding-related clusters and respiratory/allergic morbidity were investigated using multivariable logistic and linear regression models adjusted for potential confounders including early respiratory/allergic outcomes and parental history of allergy. RESULTS: Five clusters were identified among 3446 infants: Cluster 1 (45%) mainly fed with regular formula, Cluster 2 (27%) exclusively breastfed during the first 3 months, and three other clusters consuming different types of formula (pre-/probiotics for Cluster 3 [17%], pHF-HA for Cluster 4 [7%], eHF/soya for Cluster 5 [4%]). Compared to Cluster 1, children from Cluster 2 tended to have a lower risk of asthma and children from Cluster 4 had a significant lower lung function (FEV1 , FVC), higher FeNO and higher risk of sensitization at 8 years. CONCLUSION: Early pHF-HA use was negatively associated with objective measures of respiratory/allergic morbidity at school age, while children breastfed for at least 3 months seem protected against asthma at 8 years old.

Mediterranean diet and lung function, sensitization, and asthma at school age: The PARIS cohort.

BACKGROUND: The Mediterranean diet (MD) has known health benefits, but its specific impact on allergy development is unclear. As part of the PARIS birth cohort follow-up, we aimed to investigate the adherence of 8-year-old children to the MD and its association with allergic/respiratory morbidity at school age. METHODS: Diet was assessed using a food frequency questionnaire completed by the parents. Adherence to the MD was assessed based on two scores: the KIDMED index and the Mediterranean Diet Score (MDS). Current allergic diseases (asthma, rhinitis, eczema), lung function indices (FEV1 and FVC), FeNO and specific IgE levels were determined during a health check-up at 8 years. Associations between levels of adherence to the MD and respiratory/allergic morbidity were studied using multivariable logistic and linear regression models adjusted for potential confounders. RESULTS: A total of 975 children were included in the present study, 35.6% with low adherence to the MD, 55.7% with moderate adherence and 8.7% with high adherence according to the KIDMED index. High family socioeconomic status, any breastfeeding at 6 months and consumption of organic food were associated with higher adherence to the MD. Compared with low adherence, high adherence was associated with lower risk of asthma and sensitization at 8 years, as well as higher FEV1 and FVC. CONCLUSION: This study suggests a protective effect of high adherence to the MD on allergic and respiratory morbidity at school age. These results need to be confirmed by further longitudinal analyses. A healthy diet may prevent allergic and respiratory morbidity in school-aged children.

Children with uncontrolled asthma and significant reversibility might show hypoxaemia.

Asthmatic children free of exacerbation with airway obstruction may have low partial pressure of oxygen (PaO2) which can be a marker for future risk, but PaO2 is scarcely measured during pulmonary function testing. We prospectively included asthmatic children with airway obstruction referred for pulmonary function testing, including blood gas analysis (n = 51). Hypoxaemia, defined as a value lower than - 2 z-score, was present in 15 (29%) children, and 37 (72%) children had a significant reversibility after bronchodilator administration. The multivariable model showed a positive influence of baseline forced expiratory volume in 1 s (FEV1) on PaO2 (ß coefficient 0.69, [95% CI: 0.07; 1.30]; P = 0.03), whereas uncontrolled asthma and FEV1 reversibility negatively influenced it (ß coefficient - 1.59 [95% CI: - 2.74; - 0.44]; P = 0.01; and - 0.07 [95% CI: - 0.13; - 0.02]; P = 0.01, respectively). As a consequence, children with uncontrolled symptoms of asthma and FEV1 reversibility ≥ 12% were significantly more at risk of having hypoxaemia compared to children with well/partly controlled asthma or no significant reversibility of FEV1.Conclusion: Among obstructive asthmatic children without current exacerbation, hypoxaemia is more likely to be seen in children with uncontrolled asthma and a significant post-bronchodilator FEV1 reversibility, in favour of different pathophysiology and treatment requirements of their airway obstruction.What is Known:• Recommendations are to treat asthmatic children in order to control respiratory symptom and maintain normal pulmonary function.• Asthmatic children free of exacerbation may have different pathophysiology for airway obstruction (central, peripheral, inflammatory, spasticity, remodelling) and should be treated according the pathophysiology of their airway disease.What is New:• In obstructive asthmatic children free of current exacerbation, the presence of hypoxaemia (ventilation-perfusion mismatch) is influenced by asthma control and post-bronchodilator reversibility, independently of the level of baseline airway obstruction.• The presence of hypoxaemia in obstructive asthmatic children free of current exacerbation can be highly suspected by the composite index "uncontrolled asthma + FEV1reversibility ≥ 12%" which may guide treatment.

Unsupervised trajectories of respiratory/allergic symptoms throughout childhood in the PARIS cohort.

BACKGROUND: Natural course and co-occurrence of asthma, eczema, and allergic rhinitis through childhood are still not fully documented. We aim to identify and characterize profiles based on the time course, severity, and apparent triggers of respiratory/allergy symptoms in school-aged children. METHODS: Data on occurrence, severity, and triggers of asthma, rhinitis, and dermatitis symptoms were collected annually during the follow-up of the PARIS birth cohort. Children with similar symptom trajectories until 8-9 years were grouped into profiles using multidimensional (all symptoms considered simultaneously) cluster analysis. Associations between profiles and different health outcomes were analyzed using logistic or linear regression models. RESULTS: Six distinct symptomatic profiles were identified. A profile was defined by persistent dermatitis symptoms, associated with sensitization to food and aeroallergens. Two profiles were characterized by wheezing: one with early transient wheezing and the other with persistent wheezing related to doctor-diagnosed asthma, airway obstruction, and perennial aeroallergen sensitization. Three profiles were characterized by rhinitis symptoms: one non-allergic and two allergic, either with persistent rhinitis symptoms related to allergic multimorbidity and sensitization to perennial aeroallergens, or with late-onset symptoms, related to both pollen and perennial aeroallergens sensitization as well as low lung function. CONCLUSION: This study brings further insights into the developmental profiles of respiratory/allergic outcomes from birth to school age. The identified profiles clearly differed regarding objective features such as diagnosed morbidity, sensitization, or lung function measurements, thus highlighting their biologic and clinical relevance. Allergic rhinitis profiles deserve particular attention, since they were likely to be involved in multimorbidity patterns.

Loss-of-function mutations in RSPH1 cause primary ciliary dyskinesia with central-complex and radial-spoke defects.

Primary ciliary dyskinesia (PCD) is a rare autosomal-recessive respiratory disorder resulting from defects of motile cilia. Various axonemal ultrastructural phenotypes have been observed, including one with so-called central-complex (CC) defects, whose molecular basis remains unexplained in most cases. To identify genes involved in this phenotype, whose diagnosis can be particularly difficult to establish, we combined homozygosity mapping and whole-exome sequencing in a consanguineous individual with CC defects. This identified a nonsense mutation in RSPH1, a gene whose ortholog in Chlamydomonas reinhardtii encodes a radial-spoke (RS)-head protein and is mainly expressed in respiratory and testis cells. Subsequent analyses of RSPH1 identified biallelic mutations in 10 of 48 independent families affected by CC defects. These mutations include splicing defects, as demonstrated by the study of RSPH1 transcripts obtained from airway cells of affected individuals. Wild-type RSPH1 localizes within cilia of airway cells, but we were unable to detect it in an individual with RSPH1 loss-of-function mutations. High-speed-videomicroscopy analyses revealed the coexistence of different ciliary beating patterns-cilia with a normal beat frequency but abnormal motion alongside immotile cilia or cilia with a slowed beat frequency-in each individual. This study shows that this gene is mutated in 20.8% of individuals with CC defects, whose diagnosis could now be improved by molecular screening. RSPH1 mutations thus appear as a major etiology for this PCD phenotype, which in fact includes RS defects, thereby unveiling the importance of RSPH1 in the proper building of CCs and RSs in humans.

Airway Remodeling in Preschool Children with Severe Recurrent Wheeze.

RATIONALE: Airway wall structure in preschoolers with severe recurrent wheeze is poorly described. OBJECTIVES: To describe airway wall structure and inflammation in preschoolers with severe recurrent wheeze. METHODS: Flexible bronchoscopy was performed in two groups of preschoolers with severe recurrent wheeze: group 1, less than or equal to 36 months (n = 20); group 2, 36-59 months (n = 29). We assessed airway inflammation, reticular basement membrane (RBM) thickness, airway smooth muscle (ASM), mucus gland area, vascularity, and epithelial integrity. Comparisons were then made with biopsies from 21 previously described schoolchildren with severe asthma (group 3, 5-11.2 yr). MEASUREMENTS AND MAIN RESULTS: RBM thickness was lower in group 1 than in group 2 (3.3 vs. 3.9 µm; P = 0.02), was correlated with age (P < 0.01; ρ = 0.62), and was higher in schoolchildren than in preschoolers (6.8 vs. 3.8 µm; P < 0.01). ASM area was lower in preschoolers than in schoolchildren (9.8% vs. 16.5%; P < 0.01). Vascularity was higher in group 1 than in group 2 (P = 0.02) and group 3 (P < 0.05). Mucus gland area was higher in preschoolers than in schoolchildren (16.4% vs. 4.6%; P < 0.01). Inflammatory cell counts in biopsies were not correlated with airway wall structure. ASM area was higher in preschoolers with atopy than without atopy (13.1% vs. 7.7%; P = 0.01). Airway morphometrics and inflammation were similar in viral and multiple-trigger wheezers. CONCLUSIONS: In preschoolers with severe recurrent wheeze, markers of remodeling and inflammation are unrelated, and atopy is associated with ASM. In the absence of control subjects, we cannot determine whether differences observed in RBM thickness and vascularity result from disease or normal age-related development.

Forced expiratory flows' contribution to lung function interpretation in schoolchildren.

Forced expiratory flow (FEF) at low lung volumes are supposed to be better at detecting lung-function impairment in asthmatic children than a forced volume. The aim of this study was to examine whether FEF results could modify the interpretation of baseline and post-bronchodilator spirometry in asthmatic schoolchildren in whom forced expiratory volumes are within the normal range. Spirometry, with post-bronchodilator vital capacity within 10% of that of baseline in healthy and asthmatic children, was recorded prospectively. We defined abnormal baseline values expressed as z-scores <-1.645, forced expiratory volume in 1 s (FEV1) reversibility as a baseline increase >12%, FEF reversibility as an increase larger than the 2.5th percentile of post-bronchodilator changes in healthy children. Among 66 healthy and 50 asthmatic schoolchildren, only two (1.7%) children with normal vital capacity and no airways obstruction had abnormal baseline forced expiratory flow at 25-75% of forced vital capacity (FEF25-75%). After bronchodilation, among the 45 asthmatic children without FEV1 reversibility, 5 (11.1%) had an FEF25-75% increase that exceeded the reference interval. Isolated abnormal baseline values or significant post-bronchodilator changes in FEF are rare situations in asthmatic schoolchildren with good spirometry quality.

Carbon dioxide levels during polygraphy in children with sleep-disordered breathing.

PURPOSE: The recent scoring rules of the American Academy of Sleep Medicine (AASM) define hypoventilation in children as a carbon dioxide (CO2) level of >50 mmHg for >25 % of total sleep time (partial pressure of CO2 (PCO2) > 50[>25 %]). As there is no validated level of nocturnal hypoventilation with regard to end-organ damage in children, we evaluated the prevalence of hypoventilation with the AASM definition but also with a lesser degree of elevated CO2 in children with sleep-disordered breathing (SDB). METHODS: Transcutaneous CO2 (PtcCO2) was recorded during overnight polygraphy (PG). Hypoventilation was defined according to four definitions: the AASM score (PCO2 > 50[>25 %]), the peak value of PtcCO2 > 50 mmHg (PtcCO2 > 50[peak]), a percentage of PtcCO2 > 50 mmHg > 2 % of nighttime recording (PtcCO2 > 50[>2 %]) or a nocturnal PtcCO2 > 10 mmHg above waking baseline level (PtcCO2[>10 mmHg]). PtcCO2 indices were correlated to the apnoea-hypopnoea index (AHI) and oxygenation indices. RESULTS: PGs from 221 children with suspicion of obstructive sleep apnoea (72 %), neuromuscular diseases (21 %), and lung diseases (7 %) were analysed. The prevalence of hypoventilation according to PCO2 > 50[>25 %], PtcCO2 > 50[peak], PtcCO2 > 50[>2 %] and PtcCO2[>10 mmHg] were 16, 27, 31 and 52 %, respectively, and did not differ between the three diagnostic groups. Significant but weak correlations were observed between hypoventilation and AHI and oxygenation indices. CONCLUSIONS: Nocturnal hypoventilation occurs in a large number of children referred for SDB, independent of the underlying disease, when more stringent criteria than those of the AASM are used. The poor correlation between hypoventilation and AHI or oxygenation indices is in favour of CO2 being a supplemental index of SDB.

Analysis of mandibular jaw movements to assess ventilatory support management of children with obstructive sleep apnea syndrome treated with positive airway pressure therapies.

BACKGROUND: The polysomnography (PSG) is the gold-standard for obstructive sleep apnea (OSA) syndrome diagnosis and assessment under positive airway pressure (PAP) therapies in children. Recently, an innovative digital medicine solution, including a mandibular jaw movement (MJM) sensor coupled with automated analysis, has been validated as an alternative to PSG for pediatric application. OBJECTIVE: This study aimed to assess the reliability of MJM automated analysis for the assessment of residual apnea/hypopnea events during sleep in children with OSA treated with noninvasive ventilation (NIV) or continuous PAP (CPAP). METHODS: In this open-label prospective non-randomized multicentric trial, we included children aged from 5 to 18 years with a diagnosis of severe OSA. The children underwent in-laboratory PSG with simultaneous MJM monitoring and at-home recording with MJM monitoring 3 months later. Agreement between PSG and MJM analysis in measuring the residual apnea-hypopnea index (AHI) was evaluated by the Bland-Altman method. The treatment effect on residual AHI was estimated for both PSG and MJM analysis. RESULTS: Fifteen (60% males) children were included with a median age of 12 years [interquartile range 8-15]. Two (17%) were ventilated with NIV and 13 (83%) with CPAP. There was a good agreement between MJM-AHI and PSG-AHI with a median bias of -0.25 (95% CI: -3.40 to +2.04) events/h. The reduction in AHI under treatment was consistently significant across the three measurement methods: in-laboratory PSG and MJM recordings in the laboratory and at home. CONCLUSION: Automated analysis of MJM is a highly reliable alternative method to assess residual events in a small population treated with PAP therapies.

ERS International Congress 2023: highlights from the Paediatrics Assembly.

Respiratory health in children is essential for general wellbeing and healthy development in the short and long term. It is well known that many respiratory diseases in adulthood have their origins in early life, and therefore research on prevention of respiratory diseases and management of children with respiratory diseases will benefit patients during the full life course. Scientific and clinical advances in the field of respiratory health are moving at a fast pace. This article summarises some of the highlights in paediatric respiratory medicine presented at the hybrid European Respiratory Society (ERS) International Congress 2023 which took place in Milan (Italy). Selected sessions are summarised by Early Career Members of the Paediatrics Assembly (Assembly 7) under the supervision of senior ERS officers, and cover a wide range of research areas in children, including respiratory physiology and sleep, asthma and allergy, cystic fibrosis, respiratory infection and immunology, neonatology and intensive care, respiratory epidemiology and bronchology.

A BEAT-PCD consensus statement: a core outcome set for pulmonary disease interventions in primary ciliary dyskinesia.

Background: Consistent use of reliable and clinically appropriate outcome measures is a priority for clinical trials, with clear definitions to allow comparability. We aimed to develop a core outcome set (COS) for pulmonary disease interventions in primary ciliary dyskinesia (PCD). Methods: A multidisciplinary international PCD expert panel was set up. A list of outcomes was created based on published literature. Using a modified three-round e-Delphi technique, the panel was asked to decide on relevant end-points related to pulmonary disease interventions and how they should be reported. First, inclusion of an outcome in the COS was determined. Second, the minimum information that should be reported per outcome. The third round finalised statements. Consensus was defined as ≥80% agreement among experts. Results: During the first round, experts reached consensus on four out of 24 outcomes to be included in the COS. Five additional outcomes were discussed in subsequent rounds for their use in different subsettings. Consensus on standardised methods of reporting for the COS was reached. Spirometry, health-related quality-of-life scores, microbiology and exacerbations were included in the final COS. Conclusion: This expert consensus resulted in a COS for clinical trials on pulmonary health among people with PCD.