Association between upper and lower respiratory disease among patients with primary ciliary dyskinesia: an international study.

Introduction: Nearly all patients with primary ciliary dyskinesia (PCD) report ear-nose-throat (ENT) symptoms. However, scarce evidence exists about how ENT symptoms relate to pulmonary disease in PCD. We explored possible associations between upper and lower respiratory disease among patients with PCD in a multicentre study. Methods: We included patients from the ENT Prospective International Cohort (EPIC-PCD). We studied associations of several reported ENT symptoms and chronic rhinosinusitis (defined using patient-reported information and examination findings) with reported sputum production and shortness of breath, using ordinal logistic regression. In a subgroup with available lung function results, we used linear regression to study associations of chronic rhinosinusitis and forced expiratory volume in 1 s (FEV1) accounting for relevant factors. Results: We included 457 patients (median age 15 years, interquartile range 10-24 years; 54% males). Shortness of breath associated with reported nasal symptoms and ear pain of any frequency, often or daily hearing problems, headache when bending down (OR 2.1, 95% CI 1.29-3.54) and chronic rhinosinusitis (OR 2.3, 95% CI 1.57-3.38) regardless of polyp presence. Sputum production associated with daily reported nasal (OR 2.2, 95% CI 1.20-4.09) and hearing (OR 2.0, 95% CI 1.10-3.64) problems and chronic rhinosinusitis (OR 2.1, 95% CI 1.48-3.07). We did not find any association between chronic rhinosinusitis and FEV1. Conclusion: Reported upper airway symptoms and signs of chronic rhinosinusitis associated with reported pulmonary symptoms, but not with lung function. Our results emphasise the assessment and management of upper and lower respiratory disease as a common, interdependent entity among patients with PCD.

SARS-CoV-2 variants of concern in children and adolescents with COVID-19: a systematic review.

OBJECTIVES: Infections by SARS-CoV-2 variants of concern (VOCs) might affect children and adolescents differently than earlier viral lineages. We aimed to address five questions about SARS-CoV-2 VOC infections in children and adolescents: (1) symptoms and severity, (2) risk factors for severe disease, (3) the risk of infection, (4) the risk of transmission and (5) long-term consequences following a VOC infection. DESIGN: Systematic review. DATA SOURCES: The COVID-19 Open Access Project database was searched up to 1 March 2022 and PubMed was searched up to 9 May 2022. ELIGIBILITY CRITERIA: We included observational studies about Alpha, Beta, Gamma, Delta and Omicron VOCs among ≤18-year-olds. We included studies in English, German, French, Greek, Italian, Spanish and Turkish. DATA EXTRACTION AND SYNTHESIS: Two reviewers extracted and verified the data and assessed the risk of bias. We descriptively synthesised the data and assessed the risks of bias at the outcome level. RESULTS: We included 53 articles. Most children with any VOC infection presented with mild disease, with more severe disease being described with the Delta or the Gamma VOC. Diabetes and obesity were reported as risk factors for severe disease during the whole pandemic period. The risk of becoming infected with a SARS-CoV-2 VOC seemed to increase with age, while in daycare settings the risk of onward transmission of VOCs was higher for younger than older children or partially vaccinated adults. Long-term symptoms following an infection with a VOC were described in <5% of children and adolescents. CONCLUSION: Overall patterns of SARS-CoV-2 VOC infections in children and adolescents are similar to those of earlier lineages. Comparisons between different pandemic periods, countries and age groups should be improved with complete reporting of relevant contextual factors, including VOCs, vaccination status of study participants and the risk of exposure of the population to SARS-CoV-2. PROSPERO REGISTRATION NUMBER: CRD42022295207.

Ear and upper airway clinical outcome measures for use in primary ciliary dyskinesia research: a scoping review.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterised by pulmonary, otological and sino-nasal manifestations. Well-defined clinical outcome measures are needed in such rare diseases research to improve follow-up and treatments. Pulmonary outcome measures have recently been described. The aim of this study was to identify ear and upper airway outcome measures that could be used for longitudinal follow-up of individuals with PCD. METHODS: A scoping review was performed by systematically searching MEDLINE, Embase and Cochrane Database of Systematic Reviews online databases for studies published from January 1996 to March 2022 that included at least 10 adult or paediatric PCD patients and reported ear and upper airway outcomes. RESULTS: 33 studies (1794 patients) were included. 10 ear and upper airway outcomes were reported. 17 studies reported audiometry, 16 reported otoscopic findings, and 13 reported rhinoscopic findings and sinus imaging. Health-related quality of life questionnaires were performed in seven studies. There was a high variability in definitions and measurement of outcomes between studies. CONCLUSIONS: This scoping review highlights the lack of data regarding ear and upper airway outcomes in PCD. It also reports a high heterogeneity in outcome definitions or measures. We provide well-founded specific suggestions to standardise ear and upper airway outcome definitions and reporting for future PCD research studies.

Sinonasal disease among patients with primary ciliary dyskinesia: an international study.

Background: Sinonasal symptoms are a common feature of primary ciliary dyskinesia (PCD); however, literature about their severity and frequency, particularly during the life course, is scarce. Using baseline data from the Ear, nose and throat (ENT) Prospective International Cohort of PCD patients, we describe sinonasal disease in PCD. Methods: We included participants who had a routine sinonasal examination during which they completed a symptoms questionnaire. We compared frequency of reported symptoms and examination findings among children and adults, and identified characteristics potentially associated with higher risk of sinonasal disease using ordinal regression. Results: 12 centres contributed 384 participants; median age was 16 years (IQR 9-22), and 54% were male. Chronic nasal problems were the most common feature, reported by 341 (89%). More adults (33; 24%) than children (10; 4%) described hyposmia. Quality of life was moderately affected by rhinosinusitis among 136 participants with completed SNOT-22 questionnaires (median score 31; IQR 23-45). Examinations revealed nasal polyps among 51 of 345 participants (15%) and hypertrophic inferior nasal turbinates among 127 of 341 participants (37%). Facial pain was detected in 50 of 342 participants (15%). Nasal polyps, hypertrophic turbinates, deviated septum and facial pain were found more commonly in adults than children. The only characteristic associated with higher risk of sinonasal disease was age 10 years and older. Conclusions: Based on our findings, regular sinonasal examinations are relevant for patients with PCD of all ages. There is a need for improved management of sinonasal disease supported by evidence-based guidelines.

Characteristics of Otologic Disease Among Patients With Primary Ciliary Dyskinesia.

Importance: Otologic disease is common among people with primary ciliary dyskinesia (PCD), yet little is known about its spectrum and severity. Objective: To characterize otologic disease among participants with PCD using data from the Ear-Nose-Throat Prospective International Cohort. Design, Setting, and Participants: This cross-sectional analysis of baseline cohort data from February 2020 through July 2022 included participants from 12 specialized centers in 10 countries. Children and adults with PCD diagnoses; routine ear, nose, and throat examinations; and completed symptom questionnaires at the same visit or within 2 weeks were prospectively included. Exposures: Potential risk factors associated with increased risk of ear disease. Main Outcomes and Measures: The prevalence and characteristics of patient-reported otologic symptoms and findings from otologic examinations, including potential factors associated with increased risk of ear inflammation and hearing impairment. Results: A total of 397 individuals were eligible to participate in this study (median [range] age, 15.2 [0.2-72.4] years; 186 (47%) female). Of the included participants, 204 (51%) reported ear pain, 110 (28%) reported ear discharge, and 183 (46%) reported hearing problems. Adults reported ear pain and hearing problems more frequently when compared with children. Otitis media with effusion-usually bilateral-was the most common otoscopic finding among 121 of 384 (32%) participants. Retracted tympanic membrane and tympanic sclerosis were more commonly seen among adults. Tympanometry was performed for 216 participants and showed pathologic type B results for 114 (53%). Audiometry was performed for 273 participants and showed hearing impairment in at least 1 ear, most commonly mild. Season of visit was the strongest risk factor for problems associated with ear inflammation (autumn vs spring: odds ratio, 2.40; 95% CI, 1.51-3.81) and age 30 years and older for hearing impairment (41-50 years vs ≤10 years: odds ratio, 3.33; 95% CI, 1.12-9.91). Conclusion and Relevance: In this cross-sectional study, many people with PCD experienced ear problems, yet frequency varied, highlighting disease expression differences and possible clinical phenotypes. Understanding differences in otologic disease expression and progression during lifetime may inform clinical decisions about follow-up and medical care. Multidisciplinary PCD management should be recommended, including regular otologic assessments for all ages, even without specific complaints.

Physical activity, respiratory physiotherapy practices, and nutrition among people with primary ciliary dyskinesia in Switzerland - a cross-sectional survey.

AIMS OF THE STUDY: We know little about the level of physical activity, respiratory physiotherapy practices and nutritional status of people with primary ciliary dyskinesia (PCD), although these are important aspects of patients with chronic respiratory disease. We assessed physical activity, respiratory physiotherapy practices and nutritional status among people with primary ciliary dyskinesia in Switzerland, investigated how these vary by age and identified factors associated with regular physical activity. METHODS: We sent a postal questionnaire survey to people with primary ciliary dyskinesia enrolled in the Swiss PCD registry (CH-PCD), based on the standardised FOLLOW-PCD patient questionnaire. We collected information about physical activity, physiotherapy, respiratory symptoms and nutritional status. We calculated the metabolic equivalent (MET) to better reflect the intensity of the reported physical activities. To assess nutritional status, we extracted information from CH-PCD and calculated participants' body mass index (BMI). RESULTS: Of the 86 questionnaires we sent, 74 (86% response rate) were returned from 24 children and 50 adults. The median age at survey completion was 23 years (IQR [interquartile range] 15-51), and 51% were female. Among all 74 participants, 48 (65%) performed sports regularly. Children were vigorously active (median MET 9.1; IQR 7.9-9.6) and adults were moderately active (median MET 5.5; IQR 4.3-6.9). Fifty-nine participants (80%) reported performing some type of respiratory physiotherapy. However, only 30% of adults saw a professional physiotherapist, compared with 75% of children. Half of the participants had normal BMI; one child (4%) and two adults (4%) were underweight. People who were regularly physically active reported seeing a physiotherapist more often. CONCLUSIONS: Our study is the first to provide patient-reported data about physical activity, respiratory physiotherapy and nutrition among people with primary ciliary dyskinesia. Our results highlight that professional respiratory physiotherapy, exercise recommendations and nutritional advice are often not implemented in the care of people with primary ciliary dyskinesia in Switzerland. Multidisciplinary care in specialised centres by teams including physiotherapists and nutrition consultants could improve the quality of life of people with primary ciliary dyskinesia.

ERS International Congress 2021: highlights from the Paediatric Assembly.

In this review, Early Career Members of the European Respiratory Society (ERS) and the Chairs of the ERS Assembly 7: Paediatrics present the highlights in paediatric respiratory medicine from the ERS International Congress 2021. The eight scientific Groups of this Assembly cover respiratory physiology and sleep, asthma and allergy, cystic fibrosis (CF), respiratory infection and immunology, neonatology and intensive care, respiratory epidemiology, bronchology, and lung and airway development. We here describe new developments in lung function testing and sleep-disordered breathing diagnosis, early life exposures affecting pulmonary function in children and effect of COVID-19 on sleep and lung function. In paediatric asthma, we present the important role of the exposome in asthma development, and how biologics can provide better outcomes. We discuss new methods to assess distal airways in children with CF, as some details remain blind when using the lung clearance index. Moreover, we summarise the new ERS guidelines for bronchiectasis management in children and adolescents. We present interventions to reduce morbidity and monitor pulmonary function in newborns at risk of bronchopulmonary dysplasia and long-term chronic respiratory morbidity of this disease. In respiratory epidemiology, we characterise primary ciliary dyskinesia, identify early life determinants of respiratory health and describe the effect of COVID-19 preventive measures on respiratory symptoms. Also, we describe the epidemiology of interstitial lung diseases, possible consequences of tracheomalacia and a classification of diffuse alveolar haemorrhage in children. Finally, we highlight that the characterisation of genes and pathways involved in the development of a disease is essential to identify new biomarkers and therapeutic targets.

Respiratory symptoms of Swiss people with primary ciliary dyskinesia.

Background: Mostly derived from chart reviews, where symptoms are recorded in a nonstandardised manner, clinical data about primary ciliary dyskinesia (PCD) are inconsistent, which leads to missing and unreliable information. We assessed the prevalence and frequency of respiratory and ear symptoms and studied differences by age and sex among an unselected population of Swiss people with PCD. Methods: We sent a questionnaire that included items from the FOLLOW-PCD standardised questionnaire to all Swiss PCD registry participants. Results: We received questionnaires from 74 (86%) out of 86 invited persons or their caregivers (median age 23 years, range 3-73 years), including 68% adults (≥18 years) and 51% females. Among participants, 70 (94%) reported chronic nasal symptoms; most frequently runny nose (65%), blocked nose (55%) or anosmia (38%). Ear pain and hearing problems were reported by 58% of the participants. Almost all (99%) reported cough and sputum production. The most common chronic cough complications were gastro-oesophageal reflux (n=11; 15%), vomiting (n=8; 11%) and urinary incontinence (n=6; 8%). Only nine (12%) participants reported frequent wheeze, which occurred mainly during infection or exercise, while 49 (66%) reported shortness of breath, and 9% even at rest or during daily activities. Older patients reported more frequent nasal symptoms and shortness of breath. We found no difference by sex or ultrastructural ciliary defect. Conclusion: This is the first study to describe patient-reported PCD symptoms. The consistent collection of standardised clinical data will allow us to better characterise the phenotypic variability of the disease and study disease course and prognosis.

COVID-19 Vaccinations: Perceptions and Behaviours in People with Primary Ciliary Dyskinesia.

Primary ciliary dyskinesia (PCD) is a rare genetic disease that causes recurrent respiratory infections. People with PCD may be at higher risk of severe coronavirus disease 2019 (COVID-19), and therefore vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is important. We studied vaccination willingness, speed of vaccination uptake, side effects, and changes in social contact behaviour after vaccination in people with PCD. We used data from COVID-PCD, an international participatory cohort study. A COVID-19 vaccination questionnaire was emailed to participants in May 2021 and 423 participants from 31 countries replied (median age: 30 years, range 1-85 years; 261 (62%) female). Vaccination uptake and willingness were high, with 273 of 287 adults (96%) being vaccinated or willing to be in June 2021; only 4% were hesitant. The most common reason for hesitancy was fear of side effects, reported by 88%. Mild side effects were common, but no participant reported severe side effects. Half of the participants changed their social behaviour after vaccination by seeing friends and family more often. The high vaccination willingness in the study population might reflect the extraordinary effort taken by PCD support groups to inform people about COVID-19 vaccination. Clear and specific information and involvement of representatives is important for high vaccine uptake.

Study protocol: the ear-nose-throat (ENT) prospective international cohort of patients with primary ciliary dyskinesia (EPIC-PCD).

INTRODUCTION: Primary ciliary dyskinesia (PCD) is a rare, genetic, multiorgan disease with an estimated prevalence of 1 in 10 000. It affects mainly the upper and lower airways due to impaired mucociliary clearance. Almost all patients have sinonasal or otologic (ear-nose-throat, ENT) problems, although the ENT clinical phenotype may present great variability. Despite that, data on PCD ENT manifestations are scarce and based on small single-centre studies. To date, we know little about the spectrum and severity of PCD ENT disease, its association with lung disease, its course over life and its determinants of prognosis.This study protocol describes the aims and methods of the first prospective, observational, multinational cohort study focusing on ENT disease in patients with PCD. METHODS AND ANALYSIS: The ENT prospective international cohort of patients with PCD (EPIC-PCD) is a prospective standardised observational clinical cohort set up as a multinational multicentre study, embedded into routine patient care. It aims to longitudinally characterise ENT disease in patients with PCD and its association with lung disease, and to identify determinants of its prognosis. Patients of all ages, diagnosed with PCD who undergo an ENT clinical assessment at least once a year at one of the participating centres will be invited to participate. Collected data include diagnostic test results, results of ENT examinations, lung function measurements, information on management of ENT disease and patient-reported data on clinical symptoms and health-related quality of life (QoL). Data are collected using the standardised PCD-specific FOLLOW-PCD form and the validated QoL-PCD questionnaire. ETHICS AND DISSEMINATION: The study has been reviewed and approved by the Human Research Ethics Committees at all participating centres, based on local legislation. The results of the study will be published in scientific journals, presented at scientific conferences and disseminated to participants and national patient organisations. TRIAL REGISTRATION: NCT04611516.

COVID-PCD: a participatory research study on the impact of COVID-19 in people with primary ciliary dyskinesia.

COVID-PCD is a participatory study initiated by people with primary ciliary dyskinesia (PCD) who have an essential vote in all stages of the research from the design of the study to the recruitment of participants, and interpretation and communication of the study results. COVID-PCD aims to collect epidemiological data in real-time from people with PCD throughout the pandemic to describe incidence of coronavirus disease 2019 (COVID-19), symptoms and course of disease; identify risk factors for prognosis; and assess experiences, wishes and needs. The study is advertised through patient support groups and participants register online on the study website (www.covid19pcd.ispm.ch). The study invites persons of any age from anywhere in the world with a suspected or confirmed PCD. A baseline questionnaire assesses details on PCD diagnosis, habitual symptoms and COVID-19 episodes that occurred before study entry. Afterwards, participants receive a weekly follow-up questionnaire with questions on incident severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, current symptoms, social contact behaviour and physical activity. Occasional thematic questionnaires are sent out focussing on emerging questions of interest chosen by people with PCD. In case of hospitalisation, patients or family members are asked to obtain a hospital report. Results are continuously analysed and summaries put online. The study started recruitment on April 30, 2020, and 556 people with PCD completed the baseline questionnaire by November 2, 2020. The COVID-PCD study is a participatory study that follows people with PCD during the COVID-19 pandemic, helps to empower affected persons, and serves as a platform for communication between patients, physicians and researchers.