Redox Imbalance in Nasal Epithelial Cells of Primary Ciliary Dyskinesia Patients.

Background: Primary Ciliary Dyskinesia (PCD) represents a rare condition marked by an abnormal mobility pattern of cilia and flagella, resulting in impaired mucociliary clearance. This deficiency leads to recurrent infections and persistent inflammation of the airways. While previous studies have indicated heightened oxidative stress levels in the exhaled breath condensate of pediatric PCD patients, the assessment of oxidative stress within the affected respiratory tissue remains unexplored. Aims: To assess the oxidative status of human nasal epithelial cells (NECs) in PCD patients. Methods: Thirty-five PCD patients and thirty-five healthy control subjects were prospectively included in the study. Levels of reactive oxygen species (ROS), reactive nitrogen species (RNS), glutathione (GSH), intracellular Ca2+, plasma membrane potential, and oxidative damage in lipids and proteins were measured. In addition, apoptosis and mitochondrial function were analyzed by flow cytometry in NECs. Results: NECs from PCD patients showed reduced levels of apoptosis (p = 0.004), superoxide anion (O2-, p = 0.018), peroxynitrite (ONOO-, p = 0.007), nitric oxide (NO, p = 0.007), mitochondrial hydrogen peroxide (mtH2O2, p < 0.0001), and mitochondrial superoxide anion (mtO2-, p = 0.0004) and increased mitochondrial mass (p = 0.009) compared to those from healthy individuals. No significant differences were observed in oxidized proteins (p = 0.137) and the oxidized/reduced lipid ratio (p = 0.7973). The oxidative profile of NEC cells in PCD patients, according to their ciliary motility, recurrent otitis, recurrent pneumonia, atelectasis, bronchiectasis, and situs inversus, showed no statistically significant differences in the parameters studied. Conversely, patients with chronic rhinosinusitis exhibited lower levels of ONOO- than PCD patients without this condition, with no significant differences related to other symptoms. Conclusions: Our findings strongly suggest the presence of a redox imbalance, specifically leaning toward a reductive state, in PCD patients.

SARS-CoV-2 infection in children with cystic fibrosis: A cross-sectional multicenter study in Spain. New waves, new knowledge.

INTRODUCTION: The association between viral infections and pulmonary exacerbations in children with cystic fibrosis (cwCF) is well established. However, the question of whether cwCF are at a higher risk of COVID-19 or its adverse consequences remains controversial. METHODS: We conducted an observational, multicenter, cross-sectional study of cwCF infected by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) between March 2020 and June 2022, (first to sixth COVID-19 pandemic waves) in Spain. The study aimed to describe patients' basal characteristics, SARS-CoV-2 clinical manifestations and outcomes, and whether there were differences across the pandemic waves. RESULTS: During study time, 351 SARS-CoV2 infections were reported among 341 cwCF. Median age was 8.5 years (range 0-17) and 51% were female. Cases were unevenly distributed across the pandemic, with most cases (82%) clustered between November 2021 and June 2022 (sixth wave, also known as Omicron Wave due to the higher prevalence of this strain in that period in Spain). Most cwCF were asymptomatic (24.8%) or presented with mild Covid-19 symptoms (72.9%). Among symptomatic, most prevalent symptoms were fever (62%) and increased cough (53%). Infection occurring along the sixth wave was the only independent risk factor for being symptomatic. Just eight cwCF needed hospital admission. No multisystem inflammatory syndrome, persisting symptoms, long-term sequelae, or deaths were reported. CONCLUSIONS: Spanish current data indicate that cwCF do not experience higher risks of SARS-CoV-2 infection nor worse health outcomes or sequelae. Changes in patients' basal characteristics, clinical courses, and outcomes were detected across waves. While the pandemic continues, a worldwide monitoring of COVID-19 in pediatric CF patients is needed.

Hypoxia Enhances Oxidative Stress in Neutrophils from ZZ Alpha-1 Antitrypsin Deficiency Patients.

Alpha-1 antitrypsin deficiency (AATD) is a neutrophilic inflammatory disorder that may result in local hypoxia, reactive oxygen and nitrogen species (ROS/RNS) production, and increased damage in adjacent tissues. This study aims to determine the impact of hypoxia on neutrophil oxidative stress profile in AATD patients. Neutrophils were isolated from AATD patients and control volunteers and exposed to hypoxia (1% O2 for 4 h), ROS/RNS, mitochondrial parameters, and non-enzymatic antioxidant defenses measured by flow cytometry. The expression of enzymatic antioxidant defenses was determined by qRT-PCR. Our results indicate that ZZ-AATD neutrophils produce higher amounts of hydrogen peroxide, peroxynitrite, and nitric oxide and decreased levels of the antioxidant enzymes catalase, superoxide dismutase, and glutathione reductase. Likewise, our results show a decrease in mitochondrial membrane potential, indicating that this organelle could be involved in the production of the reactive species observed. No decrease in glutathione and thiol levels were observed. The accumulation of substances with high oxidative capacity would explain the greater oxidative damage observed in proteins and lipids. In conclusion, our results indicate that, compared to MM control individuals, ZZ-AATD neutrophils show increased ROS/RNS production under hypoxic conditions opening a new rationale for using antioxidant therapies to treat the disease.

Diffuse alveolar haemorrhage in children: an international multicentre study.

Background: Paediatric diffuse alveolar haemorrhage (DAH) is a rare heterogeneous condition with limited knowledge on clinical presentation, treatment and outcome. Methods: A retrospective, descriptive multicentre follow-up study initiated from the European network for translational research in children's and adult interstitial lung disease (Cost Action CA16125) and chILD-EU CRC (the European Research Collaboration for Children's Interstitial Lung Disease). Inclusion criteria were DAH of any cause diagnosed before the age of 18 years. Results: Data of 124 patients from 26 centres (15 counties) were submitted, of whom 117 patients fulfilled the inclusion criteria. Diagnoses were idiopathic pulmonary haemosiderosis (n=35), DAH associated with autoimmune features (n=20), systemic and collagen disorders (n=18), immuno-allergic conditions (n=10), other childhood interstitial lung diseases (chILD) (n=5), autoinflammatory diseases (n=3), DAH secondary to other conditions (n=21) and nonspecified DAH (n=5). Median (IQR) age at onset was 5 (2.0-12.9) years. Most frequent clinical presentations were anaemia (87%), haemoptysis (42%), dyspnoea (35%) and cough (32%). Respiratory symptoms were absent in 23%. The most frequent medical treatment was systemic corticosteroids (93%), hydroxychloroquine (35%) and azathioprine (27%). Overall mortality was 13%. Long-term data demonstrated persistent abnormal radiology and a limited improvement in lung function. Conclusions: Paediatric DAH is highly heterogeneous regarding underlying causes and clinical presentation. The high mortality rate and number of patients with ongoing treatment years after onset of disease underline that DAH is a severe and often chronic condition. This large international study paves the way for further prospective clinical trials that will in the long term allow evidence-based treatment and follow-up recommendations to be determined.

The disease-specific clinical trial network for primary ciliary dyskinesia: PCD-CTN.

Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterised by impaired mucociliary clearance leading to irreversible lung damage. In contrast to other rare lung diseases like cystic fibrosis (CF), there are only few clinical trials and limited evidence-based treatments. Management is mainly based on expert opinions and treatment is challenging due to a wide range of clinical manifestations and disease severity. To improve clinical and translational research and facilitate development of new treatments, the clinical trial network for PCD (PCD-CTN) was founded in 2020 under the framework of the European Reference Network (ERN)-LUNG PCD Core. Applications from European PCD sites interested in participating in the PCD-CTN were requested. Inclusion criteria consisted of patient numbers, membership of ERN-LUNG PCD Core, use of associated standards of care, experience in PCD and/or CF clinical research, resources to run clinical trials, good clinical practice (GCP) certifications and institutional support. So far, applications from 22 trial sites in 18 European countries have been approved, including >1400 adult and >1600 paediatric individuals with PCD. The PCD-CTN is headed by a coordinating centre and consists of a steering and executive committee, a data safety monitoring board and committees for protocol review, training and standardisation. A strong association with patient organisations and industrial companies are further cornerstones. All participating trial sites agreed on a code of conduct. As CTNs from other diseases have demonstrated successfully, this newly formed PCD-CTN operates to establish evidence-based treatments for this orphan disease and to bring new personalised treatment approaches to patients.

Incidence and Prevalence of Children's Diffuse Lung Disease in Spain.

BACKGROUND: Children's diffuse lung disease, also known as children's Interstitial Lung Diseases (chILD), are a heterogeneous group of rare diseases with relevant morbidity and mortality, which diagnosis and classification are very complex. Epidemiological data are scarce. The aim of this study was to analyse incidence and prevalence of chILD in Spain. METHODS: Multicentre observational prospective study in patients from 0 to 18 years of age with chILD to analyse its incidence and prevalence in Spain, based on data reported in 2018 and 2019. RESULTS: A total of 381 cases with chILD were notified from 51 paediatric pulmonology units all over Spain, covering the 91.7% of the paediatric population. The average incidence of chILD was 8.18 (CI 95% 6.28-10.48) new cases/million of children per year. The average prevalence of chILD was 46.53 (CI 95% 41.81-51.62) cases/million of children. The age group with the highest prevalence were children under 1 year of age. Different types of disorders were seen in children 2-18 years of age compared with children 0-2 years of age. Most frequent cases were: primary pulmonary interstitial glycogenosis in neonates (17/65), neuroendocrine cell hyperplasia of infancy in infants from 1 to 12 months (44/144), idiopathic pulmonary haemosiderosis in children from 1 to 5 years old (13/74), hypersensitivity pneumonitis in children from 5 to 10 years old (9/51), and scleroderma in older than 10 years old (8/47). CONCLUSIONS: We found a higher incidence and prevalence of chILD than previously described probably due to greater understanding and increased clinician awareness of these rare diseases.

Geographic distribution and phenotype of European people with cystic fibrosis carrying A1006E mutation.

BACKGROUND: A1006E is a Cystic Fibrosis (CF) mutation that is still not widely known. We report phenotypic features and geographic distribution of the largest cohort of people with CF (pwCF) carrying A1006E to date. METHODS: Study of European pwCF carrying A1006E mutation, included in the European CF Society Patient Registry (ECFSPR). Genotype, ancestries and all variables recorded were compared to a cohort of F508del/F508del patients. Rate of decline in percentage-of-predicted FEV1 (ppFEV1) was also analyzed using the 2010-2017 ECFSPR. RESULTS: 44 pwCF carrying A1006E were reported (59% males), median age 33 years old (3-58), 54.5% Spanish and 40.9% Italian, most with ancestry in Murcia (Spain) and Lazio (Italy) regions. Compared to F508del homozygous, A1006E-pwCF were significantly older (75% vs. 52.5% ≥ 18 years old) and diagnosed at later median age (6.98 vs. 0.29 years); showed lower rates of meconium ileus (2.33% vs. 17.7%), pancreatic insufficiency (27.91% vs. 99.26%), diabetes (2.33% vs. 21.98%), liver disease (6.98% vs. 36.72%) and Pseudomonas aeruginosa chronic colonization (30.95% vs. 42.51%); and presented better nutrition (BMI z-score 0.44 vs. -0.43) and ppFEV1 (90.8% vs. 78.6%), with 18.9% (most >40 years old) having a ppFEV1<70%. Additional ppFEV1 decline (0.96% per year) was attributed to F508del/F508del genotype (p = 0.0007). None died or needed organ transplantation during the study period. CONCLUSIONS: A1006E-pwCF are mainly of Western Mediterranean Spanish and Italian descent. When compared with F508del/F508del-pwCF, they usually have a milder form of the disease, associated with pancreatic sufficiency and slower FEV1 decline. However, some will develop progressive respiratory impairment during adulthood.

Incidence and Prevalence of Children's Diffuse Lung Disease in Spain / Incidencia y prevalencia de las neumopatías intersticiales pediátricas en España

Background Children's diffuse lung disease, also known as children's Interstitial Lung Diseases (chILD), are a heterogeneous group of rare diseases with relevant morbidity and mortality, which diagnosis and classification are very complex. Epidemiological data are scarce. The aim of this study was to analyse incidence and prevalence of chILD in Spain. Methods Multicentre observational prospective study in patients from 0 to 18 years of age with chILD to analyse its incidence and prevalence in Spain, based on data reported in 2018 and 2019. Results A total of 381 cases with chILD were notified from 51 paediatric pulmonology units all over Spain, covering the 91.7% of the paediatric population. The average incidence of chILD was 8.18 (CI 95% 6.28–10.48) new cases/million of children per year. The average prevalence of chILD was 46.53 (CI 95% 41.81–51.62) cases/million of children. The age group with the highest prevalence were children under 1 year of age. Different types of disorders were seen in children 2–18 years of age compared with children 0–2 years of age. Most frequent cases were: primary pulmonary interstitial glycogenosis in neonates (17/65), neuroendocrine cell hyperplasia of infancy in infants from 1 to 12 months (44/144), idiopathic pulmonary haemosiderosis in children from 1 to 5 years old (13/74), hypersensitivity pneumonitis in children from 5 to 10 years old (9/51), and scleroderma in older than 10 years old (8/47). Conclusions We found a higher incidence and prevalence of chILD than previously described probably due to greater understanding and increased clinician awareness of these rare diseases.

Antecedentes Las neumopatías intersticiales pediátricas, también conocidas con el acrónimo chILD (del inglés children's Interstitial Lung Diseases), es un grupo heterogéneo de enfermedades raras con morbimortalidad relevante, cuyo diagnóstico y clasificación son complejos. Los estudios epidemiológicos son escasos. El objetivo de este trabajo fue analizar la incidencia y la prevalencia de chILD en España. Métodos Estudio prospectivo observacional multicéntrico en pacientes de 0 a 18 años afectos de chILD para analizar la incidencia y la prevalencia en España, a partir de datos recogidos en 2018 y 2019. Resultados Se recogieron 381 casos de chILD entre 51 unidades de neumología pediátrica de toda España, que cubrían el 91,7% de la población pediátrica. La incidencia promedio fue 8,18 (IC 95%: 6,28-10,48) casos nuevos/millón de niños por año. La prevalencia promedio fue de 46,53 (IC 95%: 41,81-51,62) casos/millón de niños. El grupo de edad con mayor prevalencia fue el de niños menores de un año. Se observaron diferentes entidades en niños de 2 a 18 años en comparación con niños de 0 a 2 años. Los diagnósticos más frecuentes fueron: glucogenosis intersticial pulmonar primaria en neonatos (17/65), hiperplasia de células neuroendocrinas en lactantes de uno a 12 meses (44/144), hemosiderosis pulmonar idiopática en niños de uno a 5 años (13/74), neumonía por hipersensibilidad en niños de 5 a 10 años (9/51) y esclerodermia en mayores de 10 años (8/47). Conclusiones Encontramos una mayor incidencia y prevalencia de chILD que las descritas previamente, probablemente debido a un mayor conocimiento y detección de estas enfermedades raras.

Dermatomiositis clínicamente amiopática con afectación pulmonar, enfermedad excepcional / Clinically amyopathic dermatomyositis with pulmonary involvement, exceptional pathology

No disponible

Comparison of Physical Activity and Sedentary Behaviour between Schoolchildren with Cystic Fibrosis and Healthy Controls: A Gender Analysis.

The purpose of this study was to examine differences in sports participation and the levels of physical activity (PA) and sedentary behaviour (SB) between schoolchildren with cystic fibrosis (CF) and a healthy control group (CG) taking into account the gender variable. PA and SB were measured with an accelerometer for 7 consecutive days in 44 children (24 girls; 11.0 (3.2) years) with CF and 45 age-, sex-, and socioeconomic status-matched controls (24 girls; 11.1 (3.0) years). CF patients and CG did not differ in moderate-to-vigorous PA (54 (31) vs. 59 (27) min/day respectively) or in SB (558 (106) vs. 553 (92) min/day respectively). There were no differences in meeting the PA guidelines between both groups (CF: 36.4% vs. CG: 42.4%). Gender analysis revealed that boys were more active and met more PA guidelines than girls regardless of the group (CF or CG), girls with CF being the least active group (only 16.7% met PA guidelines). A possible compensatory effect was found between SB and PA only in the CF sample, as for each minute/day spent in SB the odds of meeting PA guidelines decreased by 34%. These findings suggest that promoting a reduction in SB is as important as promoting PA in the CF population, especially in girls. Health caregivers, coaches, teachers, or parents could offer appealing supervised and unsupervised physical activities, foster the adoption of active lifestyles, or incorporate PA into daily routines to improve the health of CF schoolchildren.

Implementation of a gene panel for genetic diagnosis of primary ciliary dyskinesia / Implementación de un panel de genes para el diagnóstico genético de la discinesia ciliar primaria

Introduction: Primary ciliary dyskinesia (PCD) is characterized by an alteration in the ciliary structure causing difficulty in the clearance of respiratory secretions. Diagnosis is complex and based on a combination of techniques. The objective of this study was to design a gene panel including all known causative genes, and to corroborate their diagnostic utility in a cohort of Spanish patients.Methods: This was a multicenter cross-sectional study of patients with a high suspicion of PCD according to European Respiratory Society criteria. We designed a gene panel for massive sequencing using SeqCap EZ capture technology that included 44 genes associated with PCD.Results: We included 79 patients, 53 of whom had a diagnosis of confirmed or highly probable PCD. The sensitivity of the gene panel was 81.1%, with a specificity of 100%. Candidate variants were found in some of the genes of the panel in 43 patients with PCD, 51.2% (22/43) of whom were homozygotes and 48.8% (21/43) compound heterozygotes. The most common causative genes were DNAH5 and CCDC39. We found 52 different variants, 36 of which were not previously described in the literature.Conclusions: The design and implementation of a tailored gene panel produces a high yield in the genetic diagnosis of PCD. This panel provides a better understanding of the causative factors involved in these patients and lays down the groundwork for future therapeutic approaches. (AU)

Introducción: La discinesia ciliar primaria (DCP) es una enfermedad caracterizada por una alteración en la estructura ciliar que impide el correcto aclaramiento de las secreciones respiratorias. Su diagnóstico es complejo y se basa en una combinación de técnicas. El objetivo de este estudio fue diseñar un panel de genes incluyendo todos los genes causantes conocidos y comprobar su utilidad diagnóstica en una cohorte de pacientes españoles.Métodos: Estudio transversal multicéntrico de pacientes con sospecha elevada de DCP, aplicando los criterios de la European Respiratory Society. Diseño de un panel de genes para secuenciación masiva con la tecnología de captura SeqCap EZ technology, incluyendo 44 genes relacionados con la DCP.Resultados: Se incluyó a 79 pacientes de los que 53 presentaron un diagnóstico de DCP confirmado o muy probable. La sensibilidad del panel de genes fue del 81,1% con una especificidad del 100%. Se encontraron variantes candidatas en alguno de los genes del panel en 43 de los pacientes con DCP, siendo 51,2% (22/43) homocigotos y 48,8% (21/43) heterocigotos compuestos. Los genes causales más frecuentes fueron DNAH5 y CCDC39. Encontramos 52 variantes distintas, 36 no descritas previamente en la literatura.Conclusiones: El diseño y la implementación de un panel de genes a medida tiene un alto rendimiento diagnóstico genético de la DCP, lo que permite conocer mejor la afectación causal de estos pacientes y sentar las bases para futuros abordajes terapéuticos. (AU)

Implementation of a Gene Panel for Genetic Diagnosis of Primary Ciliary Dyskinesia. / Implementación de un panel de genes para el diagnóstico genético de la discinesia ciliar primaria.

INTRODUCTION: Primary ciliary dyskinesia (PCD) is characterized by an alteration in the ciliary structure causing difficulty in the clearance of respiratory secretions. Diagnosis is complex and based on a combination of techniques. The objective of this study was to design a gene panel including all known causative genes, and to corroborate their diagnostic utility in a cohort of Spanish patients. METHODS: This was a multicenter cross-sectional study of patients with a high suspicion of PCD, according to European Respiratory Society criteria, designed around a gene panel for massive sequencing using SeqCap EZ capture technology that included 44 genes associated with PCD. RESULTS: We included 79 patients, 53 of whom had a diagnosis of confirmed or highly probable PCD. The sensitivity of the gene panel was 81.1%, with a specificity of 100%. Candidate variants were found in some of the genes of the panel in 43 patients with PCD, 51.2% (22/43) of whom were homozygotes and 48.8% (21/43) compound heterozygotes. The most common causative genes were DNAH5 and CCDC39. We found 52 different variants, 36 of which were not previously described in the literature. CONCLUSIONS: The design and implementation of a tailored gene panel produces a high yield in the genetic diagnosis of PCD. This panel provides a better understanding of the causative factors involved in these patients and lays down the groundwork for future therapeutic approaches.

Alloiococcus otitidis, ¿patógeno exclusivo del oído medio? / Alloiococcus otitidis, exclusive pathogen of the middle ear?

La bronquitis bacteriana persistente (BBP) se define como tos húmeda de más de tres semanas de evolución, aislamiento de patógeno en cultivo de una muestra de líquido broncoalveolar y desaparición de la tos con tratamiento con amoxicilina y ácido clavulánico durante al menos dos semanas. Si bien han aumentado el número de casos descritos desde su descripción en 2006, sigue siendo una enfermedad infradiagnosticada a pesar de que el diagnóstico y tratamiento precoz previenen la progresión a formas más graves, que pueden llegar a ser irreversibles. En la literatura se describen múltiples agentes etiológicos, siendo los más frecuentes Haemophilus influenzae no tipable, Streptococcus pneumoniae y Moraxella catarrhalis. No obstante, no hay ningún caso descrito de Alloiococcus otitidis como agente causal de BBP. Este microorganismo se ha aislado principalmente en patología del oído medio

Persistent bacterial bronchitis (PBB) is defined by the presence of wet cough for longer than 3 weeks, isolation of the pathogen in bronchoalveolar cultures and resolution of the cough with treatment with amoxicillin and clavulanic acid for at least two weeks. Although the number of updated cases has increased since its description in 2006, it remains an underdiagnosed disease despite the fact that early diagnosis and treatment prevents the evolution to more serious forms which can become irreversible. Multiple etiologic agents are found in the literature, the most frequent are non-typable Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis. However, there is no reported case of Alloidococcus otitidis as the causative agent of PBB. This microorganism has been isolated mainly in middle ear pathology

Immunofluorescence Analysis as a Diagnostic Tool in a Spanish Cohort of Patients with Suspected Primary Ciliary Dyskinesia.

Primary ciliary dyskinesia (PCD) is an autosomal recessive rare disease caused by an alteration of ciliary structure. Immunofluorescence, consisting in the detection of the presence and distribution of cilia proteins in human respiratory cells by fluorescence, has been recently proposed as a technique to improve understanding of disease-causing genes and diagnosis rate in PCD. The objective of this study is to determine the accuracy of a panel of four fluorescently labeled antibodies (DNAH5, DNALI1, GAS8 and RSPH4A or RSPH9) as a PCD diagnostic tool in the absence of transmission electron microscopy analysis. The panel was tested in nasal brushing samples of 74 patients with clinical suspicion of PCD. Sixty-eight (91.9%) patients were evaluable for all tested antibodies. Thirty-three cases (44.6%) presented an absence or mislocation of protein in the ciliary axoneme (15 absent and 3 proximal distribution of DNAH5 in the ciliary axoneme, 3 absent DNAH5 and DNALI1, 7 absent DNALI1 and cytoplasmatic localization of GAS8, 1 absent GAS8, 3 absent RSPH9 and 1 absent RSPH4A). Fifteen patients had confirmed or highly likely PCD but normal immunofluorescence results (68.8% sensitivity and 100% specificity). In conclusion, immunofluorescence analysis is a quick, available, low-cost and reliable diagnostic test for PCD, although it cannot be used as a standalone test.

Impact of SARS-CoV-2 infection in patients with cystic fibrosis in Spain: Incidence and results of the national CF-COVID19-Spain survey.

BACKGROUND: Given the high incidence of confirmed infection by SARS-CoV-2 and mortality by COVID-19 in the Spanish population, its impact was analysed among persons with Cystic Fibrosis (CF) as a group at risk of a worse evolution. The possible causes of the incidence observed in them are explained and how CF Units have faced this health challenge is detailed. METHODS: Retrospective descriptive observational study, for which a Spanish CF Patients with Confirmed COVID-19 Registry is created, requesting information on number of people affected between 8 March-16 May 2020 and their clinical-demographic characteristics from the CF Units participating in the European Cystic Fibrosis Society Patient Registry (ECFSPR). The accumulated incidence is calculated, compared with that of the general population. Additionally, a survey (CF-COVID19-Spain) is carried out on prevention of SARS-CoV-2 infection, workings of CF Units and possible reasons for the incidence observed. RESULTS: COVID-19 was diagnosed in eight CF patients, one of whom had received a lung transplant. The accumulated incidence was 32/10000 in CF patients and 49/10000 in the general population. General death rate was 5.85/10000 while no CF patients included in the ECFSPR died. The characteristics of those affected and the results of the survey are described. CONCLUSIONS: Despite being considered a disease at high risk of severe COVID-19, the low incidence and mortality in CF patients in Spain contrasts with the figures for the general population. The possible factors that would explain such findings are discussed, with the help of the results of the CF-COVID19-Spain survey.

Pulmonary function testing in children's interstitial lung disease.

The use of pulmonary function tests (PFTs) has been widely described in airway diseases like asthma and cystic fibrosis, but for children's interstitial lung disease (chILD), which encompasses a broad spectrum of pathologies, the usefulness of PFTs is still undetermined, despite widespread use in adult interstitial lung disease. A literature review was initiated by the COST/Enter chILD working group aiming to describe published studies, to identify gaps in knowledge and to propose future research goals in regard to spirometry, whole-body plethysmography, infant and pre-school PFTs, measurement of diffusing capacity, multiple breath washout and cardiopulmonary exercise tests in chILD. The search revealed a limited number of papers published in the past three decades, of which the majority were descriptive and did not report pulmonary function as the main outcome.PFTs may be useful in different stages of management of children with suspected or confirmed chILD, but the chILD spectrum is diverse and includes a heterogeneous patient group in all ages. Research studies in well-defined patient cohorts are needed to establish which PFT and outcomes are most relevant for diagnosis, evaluation of disease severity and course, and monitoring individual conditions both for improvement in clinical care and as end-points in future randomised controlled trials.

Primary ciliary dyskinesia and psychological well-being in adolescence.

Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disease with low prevalence in pediatrics. Health studies have not sufficiently analyzed the role of psychological variables in rare diseases such as PCD. This paper studies the psychological characteristics of a group of pediatric patients diagnosed with PCD compared to their healthy peers. The sample consisted of 48 preadolescents-adolescents, aged 9-18 years (M = 12.96; SD = 2.71), with similar distribution by sex, and 25% of the patients having dyskinesia. Clinical anxiety-depression, self-esteem and psychological well-being were evaluated using questionnaires: the Adolescent Psychological Well-being Scale (BIEPS-J), the Hospital Anxiety and Depression Scale (HADS) and the Rosenberg Self-Esteem Scale (RSE). Data were analysed using descriptive, mean comparison (t-test) and diffuse comparative qualitative analysis (QCA). The results show no differences were found between healthy and PCD patients in the variables analyzed, except for social ties showing the latter greater well-being in this aspect. In QCA models, the variables that best explained the high or low levels of well-being were depression and self-esteem, and primary ciliary dyskinesia was not a necessary condition for presenting low levels of well-being. In conclusion, our results highlight the need to explore psychological aspects in pediatric patients with rare diseases.

Spanish multicentre study on morbidity and pathogenicity of tracheal bronchus in children.

Tracheal bronchus (TRB) has been generally considered an anatomical variant of the tracheobronchial tree without a precise pathological effect. Its prevalence is estimated to be between 0.2% to 3% of all children undergoing bronchoscopy and scientific information has been limited to case reports or small case series. Our working hypothesis was that TRB could trigger by itself recurrent or persistent respiratory symptoms. The objective of this retrospective and multicentre study of children with a diagnosis of TRB, coming from the main paediatric pulmonology units of Spain, was to determine the anatomical and clinical characteristics, including comorbidities, of TRB in childhood and their impact in the patients' clinical outcomes. One hundred thirty-three patients from 13 institutions were included in the study. Mean diagnostic age was 3.4 years and flexible bronchoscopy was the initial diagnostic method in 85% of cases. All TRB were located on the right wall of the trachea: 76% in the lower third and 24% in the carina. The most common clinical manifestations were obstructive bronchitis (53.3%) and recurrent pneumonia (46.6%), usually affecting the right upper lobe. Regarding associated anomalies, 33% had tracheomalacia, 32% congenital cardiovascular malformations, 28% gastroesophageal reflux, 22.5% congenital tracheal stenosis, and 8.3% Down syndrome. This series appears to be the most extensive published to date addressing this topic and, according to our data, TRB does not appear to be a mere incidental finding but is more likely linked to a wide range of congenital anomalies and contributes by itself to the recurrent respiratory symptomatology that these children exhibit.

Cuestionario de enfermedad respiratoria crónica (CRQ-SAS): análisis de las propiedades psicométricas / Chronic Respiratory Disease Questionnaire (CRQ-SAS): Analysis of psychometric properties

Introducción. El Cuestionario de Enfermedad Respiratoria Crónica Autoadminsitrado (CRQ-SAS) es un instrumento utilizado para evaluar calidad de vida relacionada con la salud en diferentes idiomas y poblaciones adultas, aunque no en adolescentes. Este estudio analiza las propiedades psicométricas del CRQ-SAS en una muestra de pacientes adolescentes con enfermedad respiratoria crónica y las relaciona con la clínica ansioso-depresiva. Método. Para analizar propiedades psicométricas del CRQ-SAS, se realizaron análisis factoriales exploratorios y confirmatorios, para estudiar la fiabilidad y validez de la escala. Para evaluar las relaciones con la clínica ansioso-depresiva, se realizaron correlaciones y regresiones lineales múltiples con la Escala de Ansiedad y Depresión Hospitalaria. Se calcularon diferencias de medias en función de variables sociodemográficas. Resultados. El CRQ-SAS fue administrado en 280 niños y adolescentes con enfermedad respiratoria crónica de edades comprendidas entre 9 y 18 años (Media= 12,02) con una distribución similar entre varones y mujeres. Se mantuvo la estructura original de cuatro factores, se eliminaron 3 ítems de la escala original, y se obtuvo una nueva versión de 17 ítems. Esta mostró adecuadas propiedades psicométricas y de validez discriminante. La disnea y la función emocional fueron las dimensiones que mejor predijeron la clínica ansioso-depresiva. Por último, se obtuvieron baremos para la interpretación de las puntuaciones en la calidad de vida relacionada con la salud. Conclusiones. Este cuestionario, utilizado anteriormente en población adulta, puede ser un adecuado instrumento para evaluar calidad de vida relacionada con la salud en pacientes adolescentes con enfermedad respiratoria crónica.

Introduction. The Chronic Respiratory Disease Questionnaire Self-Administered Standardized (CRQ-SAS) format is used to assess health-related quality of life in different languages and adult populations, but it has not been validated in adolescents. This study analyzes the psychometric properties of the CRQ-SAS in a sample of adolescent patients with chronic respiratory disease and correlates them to anxiety and depression. Method. In relation to the CRQ-SAS psychometric properties, exploratory and confirmatory factor analyses were done to assess the instrument's reliability and validity. Correlations and multiple linear regressions with the Hospital Anxiety and Depression Scale were done to assess the relation with anxiety and depression. The mean difference was estimated based on sociodemographic outcome measures. Results. The CRQ-SAS was administered to 280 children and adolescents with chronic respiratory disease aged 9-18 years (mean=12.02), with a similar male-female distribution. The original 4-factor structure was maintained; 3 items were removed from the original scale and a new 17-item version was obtained. This showed adequate psychometric properties and discriminant validity. The dyspnea and emotional functioning domains better predicted anxiety and depression. Lastly, scales were obtained for the interpretation of health-related quality of life scores. Conclusions. This questionnaire, which has been previously used in the adult population, may be an adequate instrument to assess health-related quality of life in adolescent patients with chronic respiratory disease.