Recurrent wheezing during the first 3 years of life in a birth cohort of moderate-to-late preterm infants.

BACKGROUND: Data addressing short- and long-term respiratory morbidity in moderate-late preterm infants are limited. We aim to determine the incidence of recurrent wheezing and associated risk and protective factors in these infants during the first 3 years of life. METHODS: Prospective, multicenter birth cohort study of infants born at 32+0 to 35+0  weeks' gestation and followed for 3 years to assess the incidence of physician-diagnosed recurrent wheezing. Allergen sensitization and pulmonary function were also studied. We used multivariate mixed-effects models to identify risk factors associated with recurrent wheezing. RESULTS: A total of 977 preterm infants were enrolled. Rates of recurrent wheezing during year (Y)1 and Y2 were similar (19%) but decreased to 13.3% in Y3. Related hospitalizations significantly declined from 6.3% in Y1 to 0.75% in Y3. Independent risk factors for recurrent wheezing during Y2 and Y3 included the following: day care attendance, acetaminophen use during pregnancy, and need for mechanical ventilation. Atopic dermatitis on Y2 and male sex on Y3 were also independently associated with recurrent wheezing. Palivizumab prophylaxis for RSV during the first year of life decreased the risk or recurrent wheezing on Y3. While there were no differences in rates of allergen sensitization, pulmonary function tests (FEV0.5 ) were significantly lower in children who developed recurrent wheezing. CONCLUSIONS: In moderate-to-late premature infants, respiratory symptoms were associated with lung morbidity persisted during the first 3 years of life and were associated with abnormal pulmonary function tests. Only anti-RSV prophylaxis exerted a protective effect in the development of recurrent wheezing.

Risk factors for bronchiolitis, recurrent wheezing, and related hospitalization in preterm infants during the first year of life.

BACKGROUND: Airway diseases are highly prevalent in infants and cause significant morbidity. We aimed to determine the incidence and risk factors for respiratory morbidity in a Spanish cohort of moderate-to-late preterm (MLP) infants prospectively followed during their first year of life. METHODS: SAREPREM is a multicenter, prospective, longitudinal study. Preterm infants born at 32-35 weeks of gestation with no comorbidities were enrolled within 2 weeks of life and followed at 2-4 weeks, 6, and 12 months of age. Multivariate mixed-models were performed to identify independent risk factors associated with (i) development of bronchiolitis, (ii) recurrent wheezing, or (iii) related hospital admissions. RESULTS: Overall, 977 preterm infants were included, and 766 (78.4%) completed follow-up. Of those, 365 (47.7%) developed bronchiolitis during the first year, 144 (18.8%) recurrent wheezing, and 48 (6.3%) were hospitalized. While low birthweight, day care attendance (DCA) and school-age siblings were significantly and independently associated with both the development of bronchiolitis and recurrent wheezing, lower maternal age increased the risk for bronchiolitis and respiratory-related hospitalizations. Lastly, mechanical ventilation was associated with a higher risk of bronchiolitis and history of asthma in any parent increased the likelihood of developing recurrent wheezing. CONCLUSIONS: In this study, several non-modifiable parameters (family history of asthma, low birthweight, need for mechanical ventilation) and modifiable parameters (young maternal age, DCA, or exposure to school-age siblings) were identified as significant risk factors for the development of bronchiolitis and recurrent wheezing during the first year of life in MLP infants.

Guidelines for severe uncontrolled asthma.

Since the publication, 9 years ago, of the latest SEPAR (Spanish Society of Pulmonology and Thoracic Surgery) Guidelines on Difficult-to-Control Asthma (DCA), much progress has been made in the understanding of asthmatic disease. These new data need to be reviewed, analyzed and incorporated into the guidelines according to their level of evidence and recommendation. Recently, consensus documents and clinical practice guidelines (CPG) addressing this issue have been published. In these guidelines, specific mention will be made of what the previous DCA guidelines defined as "true difficult-to-control asthma". This is asthma that remains uncontrolled after diagnosis and a systematic evaluation to rule out factors unrelated to the disease itself that lead to poor control ("false difficult-to-control asthma"), and despite an appropriate treatment strategy (Spanish Guidelines for the Management of Asthma [GEMA] steps 5 and 6): severe uncontrolled asthma. In this respect, the guidelines propose a revised definition, an attempt to classify the various manifestations of this type of asthma, a proposal for a stepwise diagnostic procedure, and phenotype-targeted treatment. A specific section has also been included on DCA in childhood, aimed at assisting healthcare professionals to improve the care of these patients.

Is acetaminophen use associated with atopic eczema and other allergic diseases in adolescents?

Atopic Eczema (AE) is a chronic inflammatory skin disease that affects children and adults, and alters quality of life. Previous studies have suggested several socio-demographic and environmental factors related to the prevalence of AE and other allergic diseases, including acetaminophen use. In the present study, we report the rates of isolated AE, AE associated with asthma and AE associated with rhinitis among 13- to 14-year-old Spanish adolescents and the level of association of these conditions with the use of acetaminophen. We analyzed Spanish data from a cross-sectional Phase 3 study within ISAAC. A total of 28,717 adolescents completed the Phase 3 written questionnaire by answering questions for acetaminophen use and on asthma, rhinitis and AE symptoms.We observed an association between acetaminophen use and AE among the adolescents who had used acetaminophen in the previous month. Furthermore, the prevalence rate increased with the number of allergic processes: for AE alone, the adjusted Prevalence Ratio (aPR) was 1.81 and for AE associated with rhinitis or with asthma, aPRs were 2.20 and 3.03, respectively.We conclude that acetaminophen use in childhood may be an important factor associated with development and/or maintenance of AE and other allergic diseases.

Prevalence of asthma symptoms in schoolchildren, and climate in west European countries: an ecologic study.

The aim of the present study was to estimate the associations between the prevalence of asthma symptoms in schoolchildren and meteorological variables in west European countries that participated in the International Study of Asthma and Allergies in Children (ISAAC), Phase III 1997-2003. An ecologic study was carried out. The prevalence of asthma was obtained from this study from 48 centers in 14 countries, and meteorological variables from those stations closest to ISAAC centers, together with other socioeconomic and health care variables. Multilevel mixed-effects linear regression models were used. For schoolchildren aged 6-7 years, the prevalence rate of asthma decreased with an increase in mean annual sunshine hours, showed a positive association with rainy weather, and warm temperature, and a negative one with relative humidity and physician density (PD). Current wheeze prevalence was stronger in autumn/winter seasons and decreased with increasing PD. Severe current wheeze decreased with PD. For schoolchildren aged 13-14 years, the prevalence rates of asthma and current wheeze increased with rainy weather, and these rates decreased with increased PD. Current wheeze, as measured by a video questionnaire, was inversely associated with sunny weather, and nurse density. Severe current wheeze prevalence was stronger during autumn/winter seasons, decreased with PD, and indoor chlorinated public swimming pool density, and increased with rainy weather. Meteorological factors, including sunny and rainy weather, and PD may have some effect on the prevalence rates of asthma symptoms in children from west European countries.

Screening for symptoms of obstructive sleep apnea in children with severe craniofacial anomalies: assessment in a multidisciplinary unit.

OBJECTIVE: To assess the incidence of airway obstruction symptoms and the presence of obstructive sleep apnea in children with severe craniofacial anomalies by a proactive screening program using a standard questionnaire and cardiorespiratory polygraphy. PATIENTS AND METHODS: Children with severe craniofacial anomalies referred to our paediatric airway unit from February 2001 to June 2011 were eligible to be included in this retrospective, single centre study. Symptoms of airway obstruction were proactively investigated using the shorter version of the Pediatric Sleep Questionnaire (PSQ). Obstructive sleep apnea was assessed by means of cardiorespiratory polygraphy. Demographic data and reason for referral were also recorded. Primary outcomes were the prevalence of symptoms of airway obstruction and OSA. RESULTS: 44 children (24 girls) with severe craniofacial anomalies (15 Crouzon, 13 Apert, 9 Goldenhar, 5 Treacher-Collins, 2 Pfeiffer) were included, at a mean age of 5 years (range 8 months to 14 years). Reason for referral was routine follow up in 30 patients and overt OSA symptoms and signs in the remaining 14. PSQ results showed symptoms of airway obstruction in 82% of patients, being snoring the most frequent symptom (64.1%) followed by apneas (33.3%). Polygraphic studies showed inconclusive results in 8 children (18.2%), normal apnea-hypopnea index (AHI) in 16 (36.4%), mild obstructive sleep apnea in 9 (20.4%), moderate in 4 (9.1%) and severe obstructive sleep apnea in 7 (15.9%). CONCLUSIONS: Children with craniofacial anomalies have a high prevalence of symptoms of airway obstruction and obstructive sleep apnea that support a proactive screening strategy in this highly selected population.

The role of bronchoscopy in the management of patients with severe craniofacial syndromes.

PURPOSE: The purpose of this study is to assess the incidence of airway anomalies in children with severe craniofacial syndromes and to establish the role of bronchoscopy in the care of these patients. METHODS: Consecutive children with craniofacial syndromes, including both bony deformities of the skull and face, in which a bronchoscopy was performed between 1995 and 2010 were retrospectively reviewed. RESULTS: Thirty-six patients (22 boys, 14 girls; mean age, 39 months) were studied. Craniofacial synostosis was present in 21 patients (Crouzen syndrome, 11; Apert syndrome, 7, Pfeiffer syndrome, 3) and craniofacial dysostosis in 15 (Goldenhart syndrome, 8; Treacher Collins syndrome, 7). In 30 patients (83.3%), bronchoscopy was performed because of respiratory symptoms (apneic episodes, 22; respiratory distress, 13; stridor, 6; cyanosis, 1) and, in the remaining 6 (asymptomatic children), during guided tracheal intubation before a surgical procedure. Airway anomalies were found in 69.4% of patients (70% in symptomatic patients). Management consisted of tracheotomy in 13 patients, adenoidectomy/tonsillectomy in 13, glossopexy in 5, antireflux surgery in 3, and supraglottoplasty in 2. CONCLUSIONS: Airway anomalies occurred in 70% of children with severe craniofacial syndromes and respiratory symptoms. Bronchoscopy should be performed routinely in this selected group of patients, and the entire airway must be examined. Treatment should be tailored to each individual patient.

Sunny hours and variations in the prevalence of asthma in schoolchildren according to the International Study of Asthma and Allergies (ISAAC) Phase III in Spain.

The objective of this study was to estimate the relationship between the prevalence of asthma in schoolchildren aged 6-7 years and 13-14 years and the mean annual sunny hours (MASH) in Spain, and to explore predictive models for asthma prevalence. The prevalence of asthma was obtained from the International Study of Asthma and Allergies (ISAAC) Phase III 2002-2003, and climate and socio-economic variables from official sources. Nine centres were studied and a further four centres, two of which are in ISAAC, to test the predictive models. Logistic regression was used to estimate adjusted prevalence rates of asthma for each centre, and multiple regression models to study the effects of MASH and other meteorological and socio-economic variables. The adjusted prevalence rate of asthma decreased 0.6% [95% confidence interval (CI) 0.4-0.8%] for the 6-7 years group and 1.1% (95% CI 0.8-1.3%) for the 13-14 years group with an increase in the MASH of 100 h. Relative humidity was negatively associated with asthma in the older age group, and gross province product per capita (GPP) was positively associated with asthma in the younger age group. The predictive models, which included MASH, gender, relative humidity, and GPP, anticipated prevalence rates of asthma without significant differences between the levels observed and those expected in 9 of the 11 measurements carried out. The results indicate that sunny hours have a protective effect on the prevalence of asthma in schoolchildren.

Early exposure to paracetamol or to antibiotics and eczema at school age: modification by asthma and rhinoconjunctivitis.

The association between early exposure to paracetamol or to antibiotics and eczema is conflicting. This study aims to know whether the early exposure to those drugs is associated with eczema at school age, and whether the strength of the association is modified by the presence of asthma or rhinoconjunctivitis. Children aged 6-7 (n = 13908) from the International Study of Asthma and Allergies in Childhood in Spain provided data about current asthma, rhinoconjunctivitis and eczema. Parent-reported information was also obtained on paracetamol and antibiotic consumption during the first year of life. Logistic regression analysis with eczema as outcome and including exposure to paracetamol or to antibiotics, together with possible confounders, was carried out in the whole sample of children and in five different strata: no respiratory symptom and any respiratory symptom further subdivided into: asthma with rhinoconjunctivitis, asthma without rhinoconjunctivitis and rhinoconjunctivitis without asthma. In the whole sample, exposure to paracetamol was associated with eczema (aOR 1.56 [1.36-1.80]) as was antibiotic consumption (aOR 1.66 [1.43-1.92]). These associations did not substantially change after additionally adjusting for the other drug. A similar pattern was found among children without respiratory symptoms. In children with symptoms, adjusting for the other drug modified the association with paracetamol (aOR from 1.32 [1.03-1.71] to 1.09 [0.83-1.43]) but did not change that with antibiotics (aOR from 1.80 [1.38-2.35] to 1.81 [1.37-2.39]). Early exposure to paracetamol or to antibiotics is associated with an increased prevalence of eczema at school age. Asthma and/or rhinoconjunctivitis substantially modifies this association.

Asthma and rhinoconjunctivitis comorbidity: united airway disease or inherited target organs?

The idea of a united airway disease for asthma and rhinoconjunctivitis is supported by clinical and epidemiological data. However, many asthmatics do not have rhinoconjunctivitis and vice versa. The aim of this study was to investigate if the family history of a specific organ involvement is associated with the implication of the same organ in the allergic child. According to the organ involvement in either or both parents, the family history of 739 children who were skin prick positive to either Dermatophagoides pteronyssinus or D. farinae or both was defined as: asthma and rhinoconjunctivitis positive; asthma and rhinoconjunctivitis negative; asthma negative and rhinoconjunctivitis positive; and asthma positive and rhinoconjunctivitis negative. Asthma and rhinoconjunctivitis in the children were defined according to the International Study of Asthma and Allergies in Childhood questionnaire. Associations between each type of family history and the presence of asthma and/or rhinoconjunctivitis in the children were calculated and adjusted for usual confounders. Adjusted odds ratio of children having asthma, when family history included asthma, was 2.48 (1.38-4.45) when it also included rhinoconjunctivitis; and 2.13 (1.12-4.05) when it did not. However, family history of rhinoconjunctivitis was not associated with asthma in the child. Conversely, the odds ratio of children having rhinoconjunctivitis when family history included rhinoconjunctivitis was 1.84 (1.05-3.21) when it also included asthma; and 1.89 (1.23-2.89) when it did not. Family history of asthma was not associated with rhinoconjunctivitis in the child. In a population of children sensitized to mites, the organ or organs (nose and/or lung) which are implicated in parents tend to be also involved in their children.

[Air pollution and recent symptoms of asthma, allergic rhinitis, and atopic eczema in schoolchildren aged between 6 and 7 years]. / Contaminación del aire y síntomas recientes de asma, rinitis alérgica y eccema atópico en escolares de 6 y 7 años.

OBJECTIVE: The objective of the study was to analyze the relationship between air pollutants and the prevalence of recent symptoms of asthma, allergic rhinitis, and atopic eczema in schoolchildren aged between 6 and 7 years. PATIENTS AND METHODS: The prevalence of recent (previous 12 months) symptoms of allergic diseases was obtained by means of the questionnaire of the International Study of Asthma and Allergies in Childhood (ISAAC), Spain, with the participation of 7 centers (Asturias, Barcelona, Bilbao, Cartagena, La Coruña, Madrid, and Valencia) and 20 455 schoolchildren aged between 6 and 7 years, from 2002 to 2003. The pollutant detection systems of the aforementioned centers provided the mean annual concentrations of sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and total suspended particulate matter. RESULTS: The annual average concentration of SO2 showed a significant association with a higher prevalence of recent severe asthma (adjusted odds ratio [aOR] between level-1 and level-3 pollution, 1.32; 95% confidence interval [CI], 1.01-1.73), rhinitis (aOR, 1.56; 95% CI, 1.39-1.75), and rhinoconjunctivitis (aOR, 1.70; 95% CI, 1.45-2.00). The annual average concentration of CO was associated with a higher prevalence of rhinitis (aOR, 1.65; 95% CI, 1.34-2.04), rhinoconjunctivitis (aOR, 1.76; 95% CI, 1.31-2.37), and eczema (aOR, 1.55; 95% CI, 1.17-2.04). The annual average concentration for NO2 and total suspended particulate matter showed inverse associations with the prevalence of nocturnal dry cough. CONCLUSIONS: Findings suggest that air pollutants such as SO2 and CO increase the risk of recent symptoms of asthma and allergic rhinitis in schoolchildren aged between 6 and 7 years in Spain.

Influence of two different geo-climatic zones on the prevalence and time trends of asthma symptoms among Spanish adolescents and schoolchildren.

Few studies have focused on the long-term influence of the climate on the prevalence of asthma. The aim of this study is to establish the influence of geo-climatic conditions on the prevalence of asthma symptoms both in adolescents and schoolchildren, and to discover if this influence is associated with their time trends. Eight centres in Spain performed both ISAAC phases I (1994) and III (2002) in children 13-14 years old. Six of them also surveyed children 6-7 years old. For each age group and phase, about 3,000 children were surveyed per centre. This study examines the prevalence of current wheeze and severe current wheeze in two different geo-climatic zones, coast and plateau, considering their relative humidity and temperature range. In both age groups, the mean asthma prevalence on the coast, for phase I and III, was significantly higher than on the plateau. Living on the plateau was an independent protective factor for current wheeze and severe current wheeze for the two age groups. Within the coastal centres, the increase of the annual relative humidity was a statistical significant risk factor for current wheeze, the same trend existing for current severe wheeze. These effects were independent of the sex and of the phase of the study. The prevalence of asthma and severe asthma symptoms is more frequent on the coast of Spain as compared to the inner plateau. This finding was repeated both in 1994 and in 2002.

Asthma attributable to atopy: does it depend on the allergen supply?

The use of the population attributable fraction (PAF) of asthma owing to atopy has not been widely used in epidemiological studies on childhood asthma, especially to compare regions of the same country. The present study includes 1039 children from Cartagena, Spain (Mediterranean coast) and 663 from Madrid (centre of Spanish plateau) using the ISAAC phase II methodology (questionnaire and prick test to the most common allergens). While there were no differences in asthma symptoms between school children (aged 10-11 yr) from Madrid and Cartagena, atopy to any allergen was significantly higher in those from Madrid (40.9% vs. 29.3%, respectively, p < 0.0001). However, children from Madrid were mainly positive to pollen allergy whereas those from Cartagena were positive for mite allergy. PAF of all the different asthma symptoms owing to atopy (any positive skin test) and PAF of current wheezing owing to a more severe atopy (three positive wheals) were higher in children from Cartagena than those from Madrid (45.5% vs. 28.6% and 14.2% vs. 6.2%, respectively). Per cent of previous year wheezing attributable to atopy to specific allergens varied among those cities and was higher for D. pteronissinus, D. farinae, cat, and olive tree in children from Cartagena, and--conversely--higher for mixed grasses, mixed trees and Alternaria in those from Madrid. All of these differences remained significant even after adjusting for risk factors. PAF for asthma owing to atopy could be very different within the same country, probably depending on the allergen supply which may depend on environmental factors such as the climate.

Relationship of asthma and rhinoconjunctivitis with obesity, exercise and Mediterranean diet in Spanish schoolchildren.

BACKGROUND: Although several studies have investigated the influence of diet on asthma in schoolchildren, none of them has evaluated how obesity can modify this effect. A study was undertaken to evaluate the association of various foods and a Mediterranean diet with the prevalence of asthma and rhinoconjunctivitis, adjusting for obesity and exercise. METHODS: A cross-sectional study was performed in 20 106 schoolchildren aged 6-7 years from eight Spanish cities. Using the ISAAC phase III questionnaire, parents reported chest and nose symptoms, food intake, weight, height and other factors, including exercise. A Mediterranean diet score was developed. A distinction was made between current occasional asthma (COA) and current severe asthma (CSA). RESULTS: Independent of the amount of exercise, each Mediterranean score unit had a small but protective effect on CSA in girls (adjusted OR 0.90, 95% CI 0.82 to 0.98). Exercise was a protective factor for COA and rhinoconjunctivitis in girls and boys (the more exercise, the more protection). Obesity was a risk factor for CSA in girls (adjusted OR 2.35, 95% CI 1.51 to 3.64). Individually, a more frequent intake (1-2 times/week and>or=3 times/week vs never/occasionally) of seafood (adjusted ORs 0.63 (95% CI 0.44 to 0.91) and 0.53 (95% CI 0.35 to 0.80)) and cereals (adjusted OR 0.56 (95% CI 0.30 to 1.02) and 0.39 (95% CI 0.23 to 0.68)) were protective factors for CSA, while fast food was a risk factor (adjusted ORs 1.64 (95% CI 1.28 to 2.10) and 2.26 (95% CI 1.09 to 4.68)). Seafood (adjusted ORs 0.74 (95% CI 0.60 to 0.92) and 0.67 (95% CI 0.53 to 0.85)) and fruit (adjusted ORs 0.76 (95% CI 0.60 to 0.97) and 0.71 (95% CI 0.57 to 0.88)) were protective factors for rhinoconjunctivitis. CONCLUSIONS: A Mediterranean diet has a potentially protective effect in girls aged 6-7 years with CSA. Obesity is a risk factor for this type of asthma only in girls.

[Patients with cystic fibrosis managed at the cystic fibrosis units of Madrid: cross-sectional study of 387 subjects]. / Pacientes con fibrosis quística atendidos en las unidades de fibrosis quística de la Comunidad de Madrid: estudio transversal de 387 casos.

BACKGROUND AND OBJECTIVE: Our objective was to describe the clinical and genetics features of patients with cystic fibrosis (CF) attended in Madrid. PATIENTS AND METHOD: This was a descriptive, cross-sectional study of CF patients attended during 2001. Demographic, genetic, anthropometric, pancreatic insufficiency, diabetes mellitus, Pseudomonas aeruginosa colonization, lung function and body mass index (BMI) (z score) data were recorded and compared with the American CF Registry. RESULTS: 387 patients were included, most of them living in Madrid (n = 247 [63%]), 209 males (54%), with a mean age (SD) of 15.15 (10.42) years (younger than 18 years, 248, 64.24%). F508del was the most common mutation (52.8% of chromosomes) with 104 homozygous patients. Pancreatic insufficiency was present in 310 subjects (80.1%), diabetes mellitus in 30 (7.8%) and P. aeruginosa colonization in 126 (33.1%). Lung function was measured in 309 patients: mean of FEV1 and FVC predicted values (SD) was 82.5 (27.11) and 89.32 (21.89), respectively. The mean BMI z score was 0.0796 (1.18). CONCLUSIONS: CF patients from Madrid have a good nutritional status, less P. aeruginosa colonization, less pancreatic insufficiency and better lung function than those of the American CF Registry. The lower prevalence of homozygous F508del in our population may explain, at least partly, our findings.