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.

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.

Factors associated to functional recovery of left vocal fold motion impairment at two-years-old age in very preterm infants.

OBJECTIVE: To describe a cohort of neonates with left vocal fold motion impairment (LVFMI) and the factors associated to it in the neonatal period; procedures required during LVFMI treatment; and clinical outcomes at the age of 2-years. An additional objective was to study those factors which are likely to be most associated to functional recovery of LVFMI at this age. METHODS: A cohort of patients born in a tertiary care hospital with a diagnosis of left VFMI was included. Factors registered were: gender; clinical presentation at the time of examination; diagnosis of other laryngeal defects associated; data related to their neonatal period (gestational age, congenital heart defects corrective surgery required, neurologic disease, bronchopulmonary dysplasia, non-invasive ventilation required, invasive ventilation required, and tracheostomy required); treatment applied for LVFMI (tracheostomy and/or laryngeal surgery); need of language and hearing therapy; and outcomes considered by the pediatric otolaryngologist at the 2 years-old follow-up visit. RESULTS: A total of 56 patients with LVFMI diagnosis were included. Only 10 patients (17.9%) showed functional recovery from LVFMI at the age of 2 years. We found significant negative association between this recovery and language and hearing therapy (p = 0.03), which was also associated to psychomotor retardation (p < 0.001). Multivariate analysis produced similar results, being language and hearing therapy the only significant factor associated to a worse outcome (OR = 4.77 [CI95% 1.14; 20.08] p = 0.03). CONCLUSION: Psychomotor development retardation is negatively associated to functional recovery of full speech in a preterm infant's population with LVFMI diagnosis, regardless of other factors related to LVFMI etiology and severity.

Preschool Asthma Symptoms in Children Born Preterm: The Relevance of Lung Function in Infancy.

Background: The aim of the study is to assess whether lung function of infants born preterm predicts wheezing in pre-school age. Methods: A survey of the core wheezing questionnaire of the International Study on Asthma and Allergy in Children was administered to parents of preterm newborns, to whom lung function tests were performed at a corrected age of six months, and who, at the time of the survey, were between three and nine years of age. Results: Low values of all lung function parameters measured, except FVC, were predictors of wheezing at some time in life, (FEV0.5 OR: 0.62 (95%CI 0.39; 0.995); FEV0.5/FVC OR: 0.73 (0.54; 0.99)) FEF75 OR: 0.60 [0.37; 0.93]; FEF25-75 OR: 0.57 (0.37; 0.89)); and of wheezing in the past year (FEV0.5 OR: 0.36 (0.17; 0.76); FEV0.5/FVC OR: 0.59 (0.38; 0.93); FEF75 OR: 0.38 [0.19; 0.76]; FEF25-75 OR: 0.35 (0.17; 0.70). In addition, FEV0.5/FVC values lower than the lowest limit of normality, were predictive of hospital admissions due to wheezing (OR: 3.07; (1.02; 9.25)). Conclusions: Limited lung function in infancy is predictive of both future wheezing and hospitalization for a wheezing episode.

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.

Impact of early caffeine therapy in preterm newborns on infant lung function.

OBJECTIVE: To know the effect of caffeine therapy on infant lung function in preterm infants with a gestational age less than 31 weeks. MATERIAL AND METHODS: Forced vital capacity (FVC), forced expiratory volume at 0.5 seconds (FEV0.5 ), and forced expiratory flows were measured by raised volume rapid thoracoabdominal compression technique; functional residual capacity was measured by plethysmography (FRCpleth ). Compliance of the respiratory system was measured by a single interruption technique (Crs). The Student t test was used to compare lung function measurements between the two groups: treated versus nontreated with caffeine. A multivariate analysis was carried out considering each and every lung function parameter (z-score) as the dependent variable; and gender, gestational age, birth weight (z-score), corrected age, invasive mechanical ventilation (yes/no), and bronchopulmonary dysplasia (BPD) diagnosis (yes/no) as independent ones. Additionally, stratified analyses by BPD diagnosis were performed. RESULTS: The multivariate analysis showed significant higher z-scores of FVC and FEV0.5 in preterm infants treated with caffeine (P = .004 and P = .024, respectively). This result only being significant in the group of non-BPD infants (P = .021 and P = .042), after stratifying by BPD diagnosis. Differences were not found in z-scores of FEV0.5/FVC, FEF75, FEF25-75, FRCpleth, nor Crs. CONCLUSION: Lung function (FVC and FEV0.5 ) is improved in infants born under 31 weeks of gestation when treated with caffeine. This improvement is driven by the group of infants who did not suffer from BPD. Overall, our results show that there is an early beneficial effect of caffeine treatment in infant lung function.

Risk factors of non-tuberculous mycobacterial lymphadenitis in children: a case-control study.

The aim of the present study is to clarify the association between environmental exposures and non-tuberculous mycobacterial (NTM) lymphadenitis, during the last decade, in a population of children. In children up to 14 years of age in a pediatric tertiary hospital, all cases of NTM lymphadenopathy with a specific microbiological diagnosis, from January 2004 to January 2015, were reviewed. This is a case-control study (1:5 proportion), in which the prevalence of environmental factors between cases and controls was compared by means of a multivariate logistic regression analysis. A total of 24 cases were diagnosed in the aforementioned period, and 18 of them included in the case-control study. Mycobacterium avium-intracellulare was the predominant mycobacterium species isolated (83.3%). Exposure to hens showed a clear trend to be significantly associated with the disease (OR = 4.33; IC95% 0.97-19.41, p = 0.055), with no significant differences for the rest of the risk factors studied. CONCLUSION: M. avium is still the predominant bacteria causing NTM lymphadenitis in children of our region. Contact with hens has been the only risk factor for NTM lymphadenitis detected in the present study. What is Known: • M. avium is the predominant bacteria causing NTM lymphadenitis in children of our region. • There is no consensus on which environmental factors are associated with NTM lymphadenitis in children. What is New: • The only risk factor for NTM lymphadenitis found in the present study was regular contact with hens. Contact with other farm animals was not associated to NTM lymphadenitis.

Is the MARS questionnaire a reliable measure of medication adherence in childhood asthma?

OBJECTIVE: To assess the reliability of the Medication Adherence Report Scale (MARS-5) for assessing adherence in clinical practice and research. METHODS: Prospective cohort study following electronically measured inhaled corticosteroids (ICS) adherence for 1 year in 2-13-year-old children with persistent asthma. The relationship between electronically measured adherence and MARS-5 scores (ranging from 5 to 25) was assessed by Spearman's rank correlation coefficient. A ROC (receiver operating characteristic) curve was performed testing MARS-5 against electronically measured adherence. Sensitivity, specificity, positive and negative likelihood ratios of the closest MARS-5 cut-off values to the top left-hand corner of the ROC curve were calculated. RESULTS: High MARS scores were obtained (median 24, interquartile range 22-24). Despite a statistically significant correlation between MARS-5 and electronically assessed adherence (Spearman's rho = 0.47; p < 0.0001), there was considerable variation of adherence rates at every MARS-5 score. The area under the ROC curve was 0.7188. A MARS-5 score ≥23 had the best predictive ability for electronically assessed adherence, but positive and negative likelihood ratios were too small to be useful (1.65 and 0.27, respectively). CONCLUSIONS: Self-report using MARS-5 is too inaccurate to be a useful measure of adherence in children with asthma, both in clinical practice and in research.

Vitamin D and Atopic Dermatitis.

Atopic dermatitis is a chronic inflammatory skin disease that affects a high number of children worldwide. It is mainly caused by a disruption of the epidermal barrier and an abnormal immune response. Vitamin D might have some effects on the innate and adaptive immune system, generally in favour of decreasing allergenic mechanisms, as well as it might improve the skin barrier and decrease the risk of skin colonization. Thus, an increasing body of evidence links this vitamin to atopic dermatitis, although conclusions are not unanimous. Many observational studies have shown that low vitamin D serum levels are associated with a higher prevalence of this epidermal disease in childhood, but others have not. Differences in exposure time, vitamin D dose, age of participants, etc. could explain these conflicting results. Moreover, no study has been performed to date in order to determine whether variations in vitamin D levels at different ages differentially influence the risk of atopic dermatitis. A number of randomized controlled trials have tested the usefulness of systemic vitamin D as a treatment for this condition, but the results are also inconclusive. Nevertheless, topical vitamin D is not recommended because it can worsen skin lesions. Narrowband ultraviolet B is used to treat atopic dermatitis, although there is little evidence relating this type of phototherapy with variations of serum vitamin D levels or to what extent phototherapy benefits are mediated through vitamin D.