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.

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.

Recommendations for surveillance of pulmonary dysfunction among childhood, adolescent, and young adult cancer survivors: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Childhood, adolescent, and young adult (CAYA) cancer survivors are at risk of pulmonary dysfunction. Current follow-up care guidelines are discordant. Therefore, the International Late Effects of Childhood Cancer Guideline Harmonization Group established and convened a panel of 33 experts to develop evidence-based surveillance guidelines. We critically reviewed available evidence regarding risk factors for pulmonary dysfunction, types of pulmonary function testing, and timings of surveillance, then we formulated our recommendations. We recommend that CAYA cancer survivors and healthcare providers are aware of reduced pulmonary function risks and pay vigilant attention to potential symptoms of pulmonary dysfunction, especially among survivors treated with allogeneic haematopoietic stem cell transplantation, thoracic radiotherapy, and thoracic surgery. Based on existing limited evidence and current lack of interventions, our panel recommends pulmonary function testing only for symptomatic survivors. Since scarce existing evidence informs our recommendation, we highlight the need for prospective collaborative studies to address pulmonary function knowledge gaps among CAYA cancer survivors.

Diagnostic testing in people with primary ciliary dyskinesia: An international participatory study.

Diagnostic tests are important in primary ciliary dyskinesia (PCD), a rare disease, to confirm the diagnosis and characterize the disease. We compared diagnostic tests for PCD between countries worldwide, assessed whether people with PCD recall their tests, and identified factors associated with the use of tests. We used cross-sectional data from COVID-PCD-an international participatory cohort study collecting information directly from people with PCD. The baseline questionnaire inquired about tests used for PCD diagnosis. Using logistic regression, we investigated factors associated with measurement of nasal nitric oxide (nNO), biopsy for electron or video microscopy, and genetic testing. We included data from 747 participants (60% females) from 49 countries worldwide with median age 27 (interquartile range 12-44). Most (92%) reported diagnostic tests for PCD. Participants reported measurements of nNO (342; 49%), biopsy samples (561; 75%), and genetic tests (435; 58%). The reported use of individual tests, such as genetics, varied between countries from 38% in Switzerland to 68% in North America. Participant recall of test type also differed between countries with lowest recall in Switzerland. One-third (232; 36%) of participants reported all three tests (nNO, biopsy, and genetics). Recently diagnosed people reported more tests [nNO odds ratio (OR) 2.2, 95% Confidence Interval (CI) 1.5-3.2; biopsy OR 3.2, 95%CI 2.1-4.9; genetics OR 4.7, 95%CI 3.2-6.9] and those with situs abnormalities fewer tests (nNO OR 0.5, 95%CI 0.4-0.7; biopsy OR 0.5, 95%CI 0.4-0.8; genetics OR 0.7, 95%CI 0.5-0.94). Our results indicate PCD diagnostic testing differed widely around the world and many patients received incomplete diagnostic work-up based only on clinical features or single tests. People diagnosed long ago and those with situs abnormalities possibly benefit from supplementary testing to refine their diagnosis as a prerequisite for personalized medicine.

ERS International Congress 2022: highlights from the Paediatrics Assembly.

This review has been prepared by the Early Career Members and Chairs of the European Respiratory Society (ERS) Assembly 7: Paediatrics. We here summarise the highlights of the advances in paediatric respiratory research presented at the ERS International Congress 2022. The eight scientific groups of this Assembly cover a wide range of research areas, including 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 developmental biology. Specifically, we report on abstracts presented at the congress on the effect of high altitude on sleep, sleep disorders, the hypoxic challenge test, and measurements of ventilation inhomogeneity. We discuss prevention of preschool wheeze and asthma, and new asthma medications. In children with CF, we describe how to monitor the effect of CF transmembrane conductance regulator modulator therapy. We present respiratory manifestations and chronic lung disease associated with common variable immunodeficiency. Furthermore, we discuss how to monitor respiratory function in neonatal and paediatric intensive care units. In respiratory epidemiology, we present the latest news from population-based and clinical cohort studies. We also focus on innovative and interventional procedures for the paediatric airway, such as cryotherapy. Finally, we stress the importance of better understanding the molecular mechanisms underlying normal and abnormal lung development.

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.

Cigarette, shisha, and electronic smoking and respiratory symptoms in Swiss children: The LUIS study.

BACKGROUND: Smoking habits in adolescents are changing. We assessed active smoking of conventional cigarettes, e-cigarettes and shishas in Swiss schoolchildren, studied risk factors and compared respiratory problems between smokers and non-smokers. METHODS: We used data from LuftiBus in the school (LUIS), a school-based survey of respiratory health of children carried out 2013 to 2016 in the canton of Zurich, Switzerland. Participants were asked about use of cigarettes, shishas, and electronic smoking devices (ESD), and current respiratory symptoms. We studied associations between smoking and risk factors using logistic regression. RESULTS: We included 3488 schoolchildren. Among 6 to 12-year-olds, 90/1905 (5%) had smoked occasionally (

Prevalence and course of disease after lung resection in primary ciliary dyskinesia: a cohort & nested case-control study.

BACKGROUND: Lung resection is a controversial and understudied therapeutic modality in Primary Ciliary Dyskinesia (PCD). We assessed the prevalence of lung resection in PCD across countries and compared disease course in lobectomised and non-lobectomised patients. METHODS: In the international iPCD cohort, we identified lobectomised and non-lobectomised age and sex-matched PCD patients and compared their characteristics, lung function and BMI cross-sectionally and longitudinally. RESULTS: Among 2896 patients in the iPCD cohort, 163 from 20 centers (15 countries) underwent lung resection (5.6%). Among adult patients, prevalence of lung resection was 8.9%, demonstrating wide variation among countries. Compared to the rest of the iPCD cohort, lobectomised patients were more often females, older at diagnosis, and more often had situs solitus. In about half of the cases (45.6%) lung resection was performed before presentation to specialized PCD centers for diagnostic work-up. Compared to controls (n = 197), lobectomised patients had lower FVC z-scores (- 2.41 vs - 1.35, p = 0.0001) and FEV1 z-scores (- 2.79 vs - 1.99, p = 0.003) at their first post-lung resection assessment. After surgery, lung function continued to decline at a faster rate in lobectomised patients compared to controls (FVC z-score slope: - 0.037/year Vs - 0.009/year, p = 0.047 and FEV1 z-score slope: - 0.052/year Vs - 0.033/year, p = 0.235), although difference did not reach statistical significance for FEV1. Within cases, females and patients with multiple lobe resections had lower lung function. CONCLUSIONS: Prevalence of lung resection in PCD varies widely between countries, is often performed before PCD diagnosis and overall is more frequent in patients with delayed diagnosis. After lung resection, compared to controls most lobectomised patients have poorer and continuing decline of lung function despite lung resection. Further studies benefiting from prospective data collection are needed to confirm these findings.

Gastrointestinal sequelae after surgery for necrotising enterocolitis: a systematic review and meta-analysis.

OBJECTIVES: To document what types of gastrointestinal sequelae were described after surgery for necrotising enterocolitis (NEC) and to analyse their frequency. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, EMBASE and the Cochrane library (CENTRAL) from 1990 to October 2016. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included studies, which provided original data on the occurrence of gastrointestinal sequelae in patients surviving surgery for NEC. Meta-analysis and metaregression to assess heterogeneity were performed for studies including 10 or more patients with gastrointestinal strictures, recurrence of NEC, intestinal failure (IF) and adhesion ileus. RESULTS: Altogether 58 studies, including 4260 patients, met the inclusion criteria. Strictures were reported to occur in 24% (95% CI 17% to 31%) of surviving patients, recurrence of NEC in 8% (95% CI 3% to 15%), IF in 13% (95% CI 7% to 19%) and adhesion ileus in 6% (95% CI 4% to 9%). Strictures were more common following enterostomy (30%; 95% CI 23% to 37%) than after primary anastomosis (8%; 95% CI 0% to 23%) and occurred more often after enterostomy without bowel resection than with bowel resection. We found considerable heterogeneity in the weighted average frequency of all sequelae (I2 range: 38%-90%). Intestinal outcomes were poorly defined, there were important differences in study populations and designs, and the reported findings bear a substantial risk of bias. CONCLUSIONS: Gastrointestinal sequelae in neonates surviving surgery for NEC are frequent. Long-term follow-up assessing defined gastrointestinal outcomes is warranted.

Lung function in patients with primary ciliary dyskinesia: an iPCD Cohort study.

Primary ciliary dyskinesia (PCD) has been considered a relatively mild disease, especially compared to cystic fibrosis (CF), but studies on lung function in PCD patients have been few and small.This study compared lung function from spirometry of PCD patients to normal reference values and to published data from CF patients. We calculated z-scores and % predicted values for forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) using the Global Lung Function Initiative 2012 values for 991 patients from the international PCD Cohort. We then assessed associations with age, sex, country, diagnostic certainty, organ laterality, body mass index and age at diagnosis in linear regression models. Lung function in PCD patients was reduced compared to reference values in both sexes and all age groups. Children aged 6-9 years had the smallest impairment (FEV1 z-score -0.84 (-1.03 to -0.65), FVC z-score -0.31 (-0.51 to -0.11)). Compared to CF patients, FEV1 was similarly reduced in children (age 6-9 years PCD 91% (88-93%); CF 90% (88-91%)), but less impaired in young adults (age 18-21 years PCD 79% (76-82%); CF 66% (65-68%)). The results suggest that PCD affects lung function from early in life, which emphasises the importance of early standardised care for all patients.

Overweight in childhood cancer survivors: the Swiss Childhood Cancer Survivor Study.

Background: An increased risk of becoming overweight has been reported for childhood cancer survivors (CCSs), in particular leukemia survivors, although the evidence is inconclusive. Objective: We assessed the prevalence of overweight in CCSs, with a focus on leukemia survivors, compared it with their peers, and determined potential risk factors. Design: As part of the Swiss Childhood Cancer Survivor Study, we sent a questionnaire between 2007 and 2013 to all Swiss resident CCSs aged <21 y at diagnosis who had survived ≥5 y. We calculated body mass index (BMI) from medical records at diagnosis and self-reported heights and weights at survey. We calculated BMI z scores by using Swiss references for children and compared overweight prevalence in CCSs, their siblings, and the general population with the use of the Swiss Health Survey (SHS) and assessed risk factors for being overweight by using multivariable logistic regression. Results: The study included 2365 CCSs, 819 siblings, and 9591 SHS participants. At survey, at an average of 15 y after diagnosis, the prevalence of overweight in CCSs overall (26%) and in leukemia survivors (26%) was similar to that in siblings (22%) and the general population (25%). Risk factors for being overweight in CCSs were male sex (OR: 1.8; 95% CI: 1.5, 2.1), both young (OR for ages 5-14 y: 1.6; 95% CI: 1.2, 2.3) and older (range-OR for ages 25-29 y: 1.7; 95% CI: 1.2, 2.4; OR for ages 40-45 y: 4.0; 95% CI: 2.5, 6.5) age at study, lower education (OR: 1.4; 95% CI: 1.1, 1.8), migration background (OR: 1.3; 95% CI: 1.1, 1.7), and no sports participation (OR: 1.4; 95% CI: 1.1, 1.7). Risk factors for overweight were similar in peers. CCSs treated with cranial radiotherapy (≥20 Gy) were more likely to be overweight than their peers (OR: 1.6; 95% CI: 1.2, 2.2). Conclusions: The prevalence of and risk factors for being overweight are similar in long-term CCSs and their peers. This suggests that prevention methods can be the same as in the general population. An important exception is CCSs treated with cranial radiotherapy ≥20 Gy who may need extra attention during follow-up care. This study was registered at clinicaltrials.gov as NCT03297034.

Alternative inert gas washout outcomes in patients with primary ciliary dyskinesia.

The lung clearance index (LCI) derived from a nitrogen multiple breath washout test (N2-MBW) is a promising tool to assess small airways disease in primary ciliary dyskinesia, but it is difficult to apply in routine clinical settings because of its long measuring time. In this study, we aimed to assess alternative indices derived from shorter washout protocols.49 patients with primary ciliary dyskinesia (mean age 14.7±6.6 years) and 37 controls (mean age 14.3±1.4 years) performed N2-MBW and double-tracer gas (DTG) single-breath washout tests. Global (LCI and moment ratio (M2/M0)), conductive (Scond) and acinar ventilation inhomogeneity (DTG Slope III (SIII-DTG)) were determined for each individual. The main outcomes were 1) the ability to detect abnormal lung function from washout indices (>1.64 z-scores) and 2) measurement duration.The prevalence of abnormal values for LCI2.5% was 37 out of 47 (79%), for LCI5% was 34 out of 47 (72%), for M2/M0 was 34 out of 47 (72%), for Scond was 36 out of 46 (78%) and for SIII-DTG was 12 out of 35 (34%). Mean±sd duration of measurement was 19.8±11.2 min for LCI2.5%, 10.8±4.6 min for LCI5% and 8.6±2.3 min for ScondCompared to standard LCI2.5%, ventilation inhomogeneity was detected by LCI5%, moment ratio and Scond with comparable sensitivity while measurement duration was significantly shorter. Longitudinal studies will show which outcome is most suitable and practical in terms of sensitivity, duration and variability within the course of primary ciliary dyskinesia lung disease.