ABSTRACT
Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity pulmonary disease that affects both patients with cystic fibrosis (CF) and those with asthma. HLA‐DRB1 alleles have ...previously been associated with ABPA–CF susceptibility; however, HLA‐DQB1 allele associations have not been clearly established. The aim of the present study was to investigate HLA class II associations in patients with ABPA–CF and determine their roles in susceptibility or protection. Patients with ABPA–CF, patients with CF without ABPA, patients with asthma without ABPA (AST), and healthy controls were included in this study. DNA was extracted by automatic extractor. HLA‐DRB1 and ‐DQB1 genotyping was performed by the Luminex PCR‐SSOP method (One Lambda, Canoga Park, CA, USA). Allele specific PCR‐SSP was also performed by high‐resolution analysis (One Lambda). Statistical analysis was performed with SSPS and Arlequin software. Both HLA‐DRB1*5:01 and ‐DRB1*11:04 alleles occurred with greater frequency in patients with ABPA–CF than in those with AST and CF and control subjects, corroborating previously published data. On the other hand, analysis of haplotypes revealed that almost all patients with ABPA–CF lacking DRB1*15:01 or DRB1*11:04 carry either DRB1*04, DRB1*11:01, or DRB1*07:01 alleles. In the HLA‐DQB1 region, the HLA‐DQB1*06:02 allele occurred more frequently in patients with ABPA–CF than in those with AST and CF and healthy controls, whereas HLA‐DQB1*02:01 occurred less frequently in patients with ABPA–CF. These data confirm that there is a correlation between HLA‐DRB1*15:01, –DRB1*11:04, DRB1*11:01, –DRB1*04 and –DRB1*07:01 alleles and ABPA–CF susceptibility and suggest that HLA‐DQB1*02:01 is an ABPA–CF resistance allele.
The presence of co-morbidities, including underlying respiratory problems, has been identified as a risk factor for severe COVID-19 disease. Information on the clinical course of SARS-CoV-2 infection ...in children with cystic fibrosis (CF) is limited, yet vital to provide accurate advice for children with CF, their families, caregivers and clinical teams.
Cases of SARS-CoV-2 infection in children with CF aged less than 18 years were collated by the CF Registry Global Harmonization Group across 13 countries between 1 February and 7 August 2020.
Data on 105 children were collated and analysed. Median age of cases was ten years (interquartile range 6–15), 54% were male and median percentage predicted forced expiratory volume in one second was 94% (interquartile range 79–104). The majority (71%) of children were managed in the community during their COVID-19 illness. Out of 24 children admitted to hospital, six required supplementary oxygen and two non-invasive ventilation. Around half were prescribed antibiotics, five children received antiviral treatments, four azithromycin and one additional corticosteroids. Children that were hospitalised had lower lung function and reduced body mass index Z-scores. One child died six weeks after testing positive for SARS-CoV-2 following a deterioration that was not attributed to COVID-19 disease.
SARS-CoV-2 infection in children with CF is usually associated with a mild illness in those who do not have pre-existing severe lung disease.
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.
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.
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.
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).
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.
This study evaluates the impact over time of a telephone-based intervention in tobacco cessation and prevention targeting patients with cystic fibrosis (CF) in the Mediterranean region of Murcia, ...Spain. We conducted an experimental prospective study with a cohort of CF patients using an integrative smoking cessation programme, between 2008 and 2013. The target population included family members and patients from the Regional CF unit. The study included an initial tobacco exposure questionnaire, measurement of lung function, urinary cotinine levels, anthropomorphic measures and the administered intervention at specific time intervals. Of the 88 patients tracked through follow-up, active smoking rates were reduced from 10.23% to 4.55% (p = 0.06). Environmental tobacco exposure was reduced in non-smoker patients from 62.03% to 36.90% (p < 0.01) during the five year follow-up. Significant reductions in the gradient of household tobacco smoke exposure were also observed with a decrease of 12.60%, from 31.65% (n = 25/79) to 19.05% (n = 16/84) in 2013 (p = <0.01). Cotinine was significantly correlated with both active and passive exposure (p<0.01) with a significant reduction of cotinine levels from 63.13 (28.58-97.69) to 20.56 (0.86-40.27) ng/ml (p<0.01). The intervention to significantly increase the likelihood of family quitting (smoke-free home) was 1.26 (1.05-1.54). Telephone based interventions for tobacco cessation and prevention is a useful tool when applied over time. Trained intervention professionals in this area are needed in the environmental health approach for the treatment of CF.
Abstract Background There have been several studies assessing the epidemiology and effects of tobacco smoke in the cystic fibrosis (CF) population, but few address the efforts of smoking cessation ...interventions. Our objective is to present one tobacco prevention and cessation programme targeting patients with CF in the Mediterranean region of Murcia (Spain). Methods All registered patients in the Regional CF unit ( n = 105) in 2008 were included in a cross-sectional and prospective uncontrolled study of tobacco use and exposure in CF patients using a baseline and 1-year follow-up. Target population includes both patients and other family members living at home. The study included an initial telephone questionnaire, measurement of lung function, urinary cotinine levels, and several telephone counselling calls and/or personalised smoking cessation services. Results Of the 97 contacted patients, 59.8% ( n = 58) were exposed to environmental tobacco smoke (ETS), 12.4% ( n = 12) had smoked at one time, and 14.3% ( n = 8) of patients over the age of 15 actively smoked. The mean age was 31.13 (range: 19–45). Of the non-smokers ( n = 89), 56.2% reported ETS and 26.9% live with at least one smoker at home. 49.2% had urinary cotinine levels > 10 ng/ml. The correlation found between patients' cotinine levels and their reported tobacco exposure was (0.77, p < 0.0001). Active smoking by mothers during pregnancy was associated with significantly lower lung function in young CF patients (− 0.385, p = 0.04). At the 1-year follow-up, 13 individuals made attempts to stop smoking, 6 of which are now ex-smokers (12.5% of all smokers). Conclusions Smoking during pregnancy adversely affects lung function in individuals with CF. Tobacco prevention and cessation programmes are an effective and vital component for CF disease management. The trained professionals in prevention and smoking cessation services could provide patients with adequate follow-up, integrating an environmental health approach into CF patients' healthcare.
In patients with cystic fibrosis, bronchial hyperreactivity is a common finding that has not been conclusively associated with atopy. The objective of the present study was to determine the ...relationship between chronic colonization or infection with
Pseudomonas aeruginosa and bronchial hyperreactivity in a group of patients with cystic fibrosis.
A nonspecific histamine bronchial provocation test was administered to a group of 32 cystic fibrosis patients with a mean (SD) age of 11.25 (3.7) years. The presence of atopy and of chronic colonization or infection with
P aeruginosa was also studied.
Nine of the 32 patients (28.1%) studied showed bronchial hyperreactivity. The clinical status of these 9 patients was significantly worse and all were colonized or infected with
P aeruginosa. Atopy was present in 17 of the 32 patients (53.1%) in the study group, but in only 3 of the 9 patients (33.3%) with bronchial hyperreactivity. Bronchial hyperreactivity was significantly associated with colonization or infection with
P aeruginosa (
P<.001), but not with atopy (
P=.12). In the patients without atopy, colonization was significantly associated with bronchial hyperreactivity (
P=.017). In the group with normal lung function (forced expiratory volume in 1 second ≥80%) this association was also significant (
P=.044), while the association between bronchial hyperreactivity and atopy was not (
P=.11).
The results of the present study suggest that in patients with cystic fibrosis, bronchial hyperreactivity may be associated with colonization or infection with
P aeruginosa, and that this may be a more important risk factor for bronchial hyperreactivity than atopy.
La hiperreactividad bronquial (HRB) es un hallazgo común en la fibrosis quística (FQ), que no se ha relacionado de forma concluyente con la atopia. El objetivo del estudio ha sido investigar la relación existente entre la colonización-infección crónica por
Pseudomonas aeruginosa y la HRB en un grupo de pacientes con FQ.
Se realizó la prueba de broncoprovocación inespecífica con histamina a un grupo de 32 pacientes con FQ cuya edad media ± desviación estándar era de 11,25 ± 3,7 años. Además se investigó en estos pacientes la existencia de atopia y colonización-infección crónica por
P. aeruginosa.
De los 32 pacientes estudiados, se encontró HRB en 9 (28,1%), cuya situación clínica era significativamente peor. Estos 9 pacientes con HRB presentaron todos colonización-infección crónica por
P. aeruginosa. Tenían atopia 17 pacientes (53,1%) de la muestra estudiada, pero sólo 3 (33,3%) de los 9 con HRB. La HRB se asoció significativamente con la colonización-infección crónica por
P. aeruginosa (p < 0,001), pero no con la atopia (p = 0,12). Entre los pacientes sin atopia, la colonización se asoció significativamente con HRB (p = 0,017). Además, en el grupo de pacientes con función pulmonar normal (volumen espiratorio forzado en el primer segundo ≥ 80%) esta asociación fue también significativa (p = 0,044), mientras que la asociación entre HRB y atopia no lo fue (p = 0,11).
Los resultados del presente estudio indi-can que en pacientes con FQ la HRB podría estar relacionada con la colonización-infección crónica por
P. aeruginosa, que podría ser un factor de riesgo de HRB más importante que la atopia.
Abstract Mutation epidemiology in each ethnic group is important for cystic fibrosis diagnosis and genetic counselling. To date, little has been reported on the prevalence of cystic fibrosis in the ...Ecuadorian population where the mutation distribution appears to differ from that of Europe. We present a series of four Ecuadorian patients homozygous for the H609R mutation in the CFTR gene. This is the first report of detection of this mutation in the Ecuadorian population. Taking advantage of the homozygous status of the patients, an evaluation of the most important clinical parameters is presented. From the diagnostic point of view, the information provided by our study is of relevance in designing an appropriate strategy for genetic testing of patients in Ecuador and in European countries where immigration from Ecuador is common.
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