María Dolores Pastor-Vivero

Is the effect of prenatal paracetamol exposure on wheezing in preschool children modified by asthma in the mother

Background: There seems to be an association between paracetamol consumption during late pregnancy and the prevalence of wheezing in infancy and childhood. The aim of the present study is to determine whether the aforementioned association is modified by the presence of asthma in the mother. Methods: A total of 1,741 children aged 3–5 years from an epidemiological survey performed in the province of Murcia (Spain) were included in the analysis. Data on paracetamol consumption (never, at least once during pregnancy or at least once per month during pregnancy), wheezing symptoms in the offspring (according to the International Study of Asthma and Allergies in Childhood protocol) and the presence of asthma in the mother, together with other known risk factors for asthma, were obtained by means of a questionnaire. Results: The mean age of the children was 4.08 ± 0.8 years and 51.1% were males. The overall prevalence of current wheezing was 20.2%. The frequency of paracetamol usage was similar among asthmatic and non-asthmatic mothers, and only a small proportion of them took this drug at least once a month (13.8% of asthmatics and 11.0% of non-asthmatics). Compared to the mothers who never took paracetamol, there was a significant association between the mother having taken paracetamol at least once per month during pregnancy and the offspring suffering from wheezing at preschool age, but only among non-asthmatic mothers (odds ratio 1.94, 95% confidence interval 1.34–2.79 vs. odds ratio 1.05, 95% confidence interval 0.21–5.08). This association was maintained after controlling for potential confounders (odds ratio 1.74, 95% confidence interval 1.15–2.61). Conclusions: The frequent usage of paracetamol during pregnancy is associated with the prevalence of wheezing in offspring during preschool years. Asthma in the mother might modify this association.

HLA-DRB1 and HLA–DQB1 genes on susceptibility to and protection from allergic bronchopulmonary aspergillosis in patients with cystic fibrosis

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.

Do risk factors for persistent asthma modify lung function in infants and young children with recurrent wheeze

There is very limited information on how the risk of persistent asthma in recurrent wheezing (RW) infants modifies their lung function early in life. The aim of this study is to compare lung function of RW infants and young children with a positive or negative asthma predictive index (API), an index previously used to anticipate asthma persistence into childhood and adolescence.

Association between chronic colonization or infection with Pseudomonas aeruginosa and bronchial hyperreactivity in patients with cystic fibrosis

OBJECTIVE 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. PATIENTS AND METHODS 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. RESULTS 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). CONCLUSIONS 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.

CFTR H609R mutation in Ecuadorian patients with cystic fibrosis

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.

Seguimiento a largo plazo de un programa de prevención y cesación tabáquica en pacientes con fibrosis quística

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.

R248G cystic fibrosis transmembrane conductance regulator mutation in three siblings presenting with recurrent acute pancreatitis and reproductive issues: a case series

BackgroundMutational combinations of the cystic fibrosis transmembrane conductance regulator, CFTR, gene have different phenotypic manifestations at the molecular level with varying clinical consequences for individuals possessing such mutations. Reporting cystic fibrosis transmembrane conductance regulator mutations is important in understanding the genotype-phenotype correlations and associated clinical presentations in patients with cystic fibrosis. Understanding the effects of mutations is critical in developing appropriate treatments for individuals affected with cystic fibrosis, non-classic cystic fibrosis, or cystic fibrosis transmembrane conductance regulator-related disorders. This is the first report of related individuals possessing the R248G missense cystic fibrosis transmembrane conductance regulator mutation and we present their associated clinical histories.Case presentationAll three patients are of Spanish descent. Deoxyribonucleic acid analysis revealed that all three siblings possessed a novel c.742A>G mutation, resulting in a p.Arg248Gly (R248G) amino acid change in exon 6 in trans with the known N1303K mutant allele. Case 1 patient is a 39-year-old infertile man presenting with congenital unilateral absence of the vas deferens and recurrent episodes of epigastric pain. Case 2 patient is a 32-year-old woman presenting with periods of infertility, two previous spontaneous abortions, recurrent epigastric pain, and recurrent pancreatitis. Case 3 patient is a 29-year-old woman presenting with recurrent pancreatitis and epigastric pain.ConclusionsWe report the genotype-phenotype correlations and clinical manifestations of a novel R248G cystic fibrosis transmembrane conductance regulator mutation: congenital unilateral absence of the vas deferens in males, reduced female fertility, and recurrent acute pancreatitis. In addition, we discuss the possible functional consequences of the mutations at the molecular level.

Cystic fibrosis treatment: targeting the basic defect

ABSTRACT Introduction: Cystic Fibrosis (CF) is a disease caused by different class mutations in the CF transmembrane conductance regulator (CFTR) gene. It can therefore benefit from a personalized medicine approach based on the individual genotype of each patient. Areas covered: This review provides a detailed overview of the current major development of new CF treatments that target the basic CF defect. The review summarizes gene therapy, mRNA repair strategies, read-through agents, and CFTR-modulators (potentiators, correctors, stabilizers, amplifiers and different combination therapies). Expert opinion: We are currently perhaps at the most exciting stage in the history of CF, with the potential to cure the disease now on the horizon. The good results obtained with ivacaftor in patients with at least one gating mutation have encouraged researchers to develop agents targeting the basic CF defect; such agents are designed for use as monotherapy or combination therapy in patients with other genotypes. However, disease aspects such as pharmacoeconomics, drug–drug interactions, use in infants, or the need for additional endpoints in future clinical trials, may ultimately hinder research and the potential availability of novel drugs for CF patients.