Recurrent Wheezing Research Articles

Breastfeeding and wheeze-related outcomes in high-risk infants: A systematic review and meta-analysis

The risk of wheezing is high in infancy and is heightened in infants with a family history of asthma/atopy. The role of breastfeeding in influencing respiratory health for these high-risk infants is unclear. To systematically appraise evidence for the association between breastfeeding and wheeze incidences and severity in high-risk infants. Studies identified through electronic databases and reference lists were eligible if they assessed breastfeeding and respiratory outcomes in infants with a family history of asthma/atopy. The primary outcome was wheeze incidences in the first year of life. Secondary outcomes were wheeze incidences in the first 6 months of life, indicators of wheeze severity (recurrent wheeze, health-care utilization, and medication use), and other wheeze-related outcomes [bronchiolitis, pneumonia, croup, and incidence of lower respiratory tract infection (LRTI)] up to 12 months old. Meta-analyses were conducted where possible. Of 1843 articles screened, 15 observational studies met the inclusion criteria. Breastfeeding was associated with 32% reduced odds of wheezing during the first year of life (ever vs. never: OR, 0.68; 95% CI: 0.53, 0.88; n=9 studies); this association was even stronger in the first 6 months (OR, 0.45; 95% CI: 0.27, 0.75; n=5 studies). Breastfeeding for a "longer" versus "shorter" time (approximately longer vs. shorter than 3 months) was associated with 50% reduced odds of wheezing at the age of 6 months (OR, 0.50; 95% CI: 0.39, 0.64; n=3 studies). Breastfeeding was associated with reduced odds of wheezing in high-risk infants, with the strongest protection in the first 6 months. More research is needed to understand the impact of breastfeeding intensity on wheezing and to examine additional respiratory outcomes, including wheeze severity. This review was registered at PROSPERO as CRD42019118631.

Association between house renovation during pregnancy and wheezing in the first year of life: The Japan environment and children's study

BackgroundWheezing is a common symptom in infants, which may occasionally develop into asthma. There are many factors related to infant wheezing, including anatomical features, viral infections, and passive smoking. There are only a few reports on the association between renovation and pregnancy worldwide, and reports on this association are inadequate in Japan. This study aimed to examine the association between house renovation and new construction during pregnancy and wheezing in infants during the first year of life using data from the Japan Environment and Children's Study (JECS). MethodsData of pregnant women registered in JECS were collected using self-administered questionnaires during the second/third trimester and 1 month after delivery. Childbirth records were completed by the doctors. Similarly, wheezing in infants was evaluated using self-administered questionnaires 1 year after birth. Logistic regression analysis was used to determine the primary outcome. ResultsIn total, 75,731 infants, excluding those with unknown gender, who were not singleton infants, and who relocated during pregnancy and the first month of life, were examined in this study. Renovation during pregnancy increased the prevalence of wheezing (odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.20–1.48) and recurrent wheezing (OR: 1.22, 95% CI: 1.00–1.48) in the first year of life. The relationship between new construction during pregnancy and wheezing in infants was insignificant (OR: 0.98, 95% CI: 0.90–1.06). ConclusionsRenovation during pregnancy may be a risk factor for wheezing in infants, and should be avoided.

Early Life Exposure to Tris(2-butoxyethyl) Phosphate (TBOEP) Is Related to the Development of Childhood Asthma

We investigated the association between exposure to 29 organophosphate esters (OPEs) and the onset of childhood asthma and recurrent wheeze. Using a case-cohort design nested in the Canadian CHILD ...

The Use of Infant Pulmonary Function Tests in the Diagnosis of Neuroendocrine Cell Hyperplasia of Infancy

Infant pulmonary function tests (iPFTs) in subjects with neuroendocrine cell hyperplasia of infancy (NEHI) have demonstrated substantial expiratory airflow obstruction and air trapping. Can indices from iPFTs be used in the diagnosis of NEHI? This is an observational case-control study evaluating iPFT results from a registry of patients assessed at the Hadassah Hebrew University Medical Center between 2008 and 2018. iPFTs results in infants with NEHI were compared to two disease control infant groups (infants evaluated for recurrent wheezing and infants evaluated due to prematurity) and a spirometry control group of infants with normal expiratory airflow, using the Kruskal-Wallis test. Receiver operating characteristic (ROC) curves were used to assess the diagnostic accuracy of iPFT indices. We evaluated iPFT data in 481 infants (15, NEHI; 292, wheezing; 128, premature; and 46, spirometry control group). Infants with NEHI had significantly increased trapped air volumes (median functional residual capacity measured with infant whole-body plethysmography [FRCpleth] was 199%predicted; median ratio of residual volume to total lung capacity was 59%predicted) when compared with results in all evaluated groups of infants (P< .001), including multiple pairwise comparisons. Airflow limitation was demonstrated in infants with NEHI when compared with the infants in the spirometry control group but was similar to the two disease control groups. FRCpleth had the best discriminatory ability for NEHI diagnosis, with an FRCpleth≥ 150%predicted demonstrating a ROC of 0.91 (95%CI, 0.82-1.00), sensitivity of 86.7%(95%CI, 59.5%-98.3%), and specificity of 95.5%(95%CI, 93.2%-97.3%). Findings on iPFTs of markedly increased air trapping, out of proportion to the degree of airflow limitation, are characteristic of infants with NEHI. iPFT results demonstrating an FRCpleth≥ 150%predicted are highly specific for NEHI and may aid in early diagnosis. Further research is required to confirm these findings in a prospective cohort and to understand the pathophysiologic explanation for these findings.

Determinants of blood eosinophilia in moderate and severe asthmatic patients during childhood: Evidence from the severe asthma molecular phenotype (SAMP) cohort.

Asthma is a heterogeneous disease in which the interaction between genetic and environmental factors plays a major role. The significance of blood eosinophil is unclear. The aim of the study was to determine the significance of blood eosinophil count in moderate-to-severe asthmatic children of preschool age and school age. This was a prospective cross-sectional study performed from 2011 to 2015 including children from the severe asthma molecular phenotype (SAMP) cohort at Trousseau Hospital (Paris, France). We included children with severe and moderate asthma, or severe and moderate recurrent wheeze, aged from 1 to 15years at the time of exploration. We analyzed data from 402 children: 248 of preschool age and 154 of school age. Blood eosinophil count third quartile thresholds were 322 and 600cells/μL for the preschool- and school-age groups, respectively. In multivariate analysis, a blood eosinophil count over this threshold was associated with elevated total IgE (OR=5.33, P<.01), multiple hospitalizations for asthma attacks (OR=4.96, P=.03), and a maternal history of asthma (OR=4.91, P=.01) in preschool children; and with staphylococcal toxin-specific IgE (OR=2.75, P=.03) in children of school age. Random forest analysis reinforced these results. High blood eosinophil count is linked to both atopic features and control of asthma with different parameters associated with these features depending on age.

Distinct lung function and bronchodilator responses between term and preterm young children with recurrent wheezing

Recurrent or unresolved wheezing is a common complaint in certain young children populations, especially those born preterm. Using infant lung function testing, we aimed to distinguish the differences between term and preterm young children with recurrent wheezing. Children under 2 years of corrected age were enrolled if they had 3 or more wheezing episodes during the enrollment period. Healthy term controls of comparable age were also recruited for reference. Measurements of lung function were made, including tidal breathing, passive respiratory mechanics, and forced tidal and raised-volume expiration. For children with recurrent wheezing, raised-volume forced expiration was repeated after an adequate delivery of bronchodilator nebulization was achieved. In total, 68 young children (40 with recurrent wheezing and 28 healthy controls) were recruited. Among children with recurrent wheezing, 23 preterm children (preterm group), and 17 term children (term group) were enrolled. Compared with healthy controls, both the term and preterm groups had lower lung function as measured by absolute values and z scores. The term group performed worse than the preterm group with regard to forced vital capacity, forced expiratory volume at 0.5s (FEV0.5), and peak expiratory flow. Following bronchodilator nebulization, the term group had significantly higher increases in FEV0.5 and forced mid-expiratory flow than the preterm group. Young children with recurrent wheezing, especially term infants, demonstrated lower lung function than healthy controls. Moreover, the term group evidenced greater responsiveness to bronchodilators than the preterm group. The distinct bronchodilator responses may offer further information to guide the diagnosis and treatment of young children with recurrent wheezing.

Proximity to Major Roads and Risks of Childhood Recurrent Wheeze and Asthma in a Severe Bronchiolitis Cohort.

Air pollution exposures have been suggested as risk factors for childhood respiratory diseases. We investigated proximity to major roads, an indicator of air pollution exposure, and its associations with childhood recurrent wheeze and asthma. We used data from a multicenter prospective cohort study of 921 infants hospitalized for bronchiolitis and recruited from 14 U.S. states. Primary exposure was residential proximity to the nearest major road at birth through age 3 years. Residential distance from nearest major road was divided into four categories: <100, 100–200, 201–300, and >300 m. Outcomes were parent-reported recurrent wheeze by age 3 years and asthma by age 5 years. Associations between residential proximity to major roads and respiratory outcomes were investigated using multivariable Cox proportional hazards modeling and logistic regression, adjusted for confounders. Out of 920 participants with home address data, pooled estimates identified 241 (26%) participants resided within 300 m of a major road, 296 (32%) developed recurrent wheeze by age 3, and 235 out of 858 participants (27%) developed asthma by 5 years. Participants who resided close to a major road had the highest risk of recurrent wheeze (adjusted hazards ratio for <100 m, 1.59, 95%CI: 1.08–2.33) and asthma (adjusted odds ratio for 201–300 m, 1.62, 95%CI: 1.16–2.25), compared to those residing >300 m from a major road. Proximity to major roads is associated with increased risks of recurrent wheeze and asthma in young children.

Is ethnicity a 'treatable trait' in asthma?

Is ethnicity a 'treatable trait' in asthma?

Novel Treatment-Refractory Preschool Wheeze Phenotypes Identified by Cluster Analysis of Lung Lavage Constituents

Preschool children with treatment-refractory wheeze often require unscheduled acute care. Current guidelines advise treatment of persistent wheeze with inhaled corticosteroids. Alternative treatments targeting structural abnormalities and specific inflammatory patterns could be more effective. To apply unsupervised analysis of lung lavage (bronchoalveolar lavage [BAL]) variables to identify clusters of preschool children with treatment-refractory wheeze. A total of 155 children 6 years or younger underwent bronchoscopy with BAL for evaluation of airway structure, inflammatory markers, and pathogens. Variables were screened with factor analysis and sorted into clusters by Ward's method, and membership was confirmed by discriminant analysis. The model was repeatable in a 48-case validation sample and accurately classified 86% of cases. Cluster 1 (n= 60) had early-onset wheeze, 85% with structural abnormalities, mostly tracheamalacia, with low total IgE and agranulocytic BAL. Cluster 2 (n= 42) had later-onset wheeze, the highest prevalence of gastroesophageal reflux, little atopy, and two-third had increased BAL lipid-laden macrophages. Cluster 3 (n= 46) had mid-onset wheeze, low total IgE, and two-third had BAL viral transcripts, predominately human rhinovirus, with BAL neutrophilia. Cluster 4 (n= 7) was older, with high total IgE, blood eosinophilia, and mixed BAL eosinophils and neutrophils. Preschool children with recurrent wheeze refractory to inhaled corticosteroid treatment include 4 clusters: airway malacia, gastroesophageal reflux, indolent human rhinovirus bronchoalveolitis, and type-2high inflammation. The results support the risk and cost of invasive bronchoscopy to diagnose causes of treatment-refractory wheeze and develop novel therapies targeting airway malacia, human rhinovirus infection, and BAL neutrophilia in preschool children.

Evaluation of pulmonary complications and affecting factors in children for repaired esophageal atresia and tracheoesophageal fistula

IntroductionRecurrent pulmonary infections, wheezing and stridor due to swallowing dysfunction, esophageal dysmotility, gastroesophageal reflux, tracheomalacia and bronchomalacia are frequently seen complications after esophageal atresia and tracheo-esophageal fistula (EA-TEF) surgeries. This study aimed to investigate the frequency and causes of respiratory problems and to evaluate the factors that affect respiratory morbidity in patients who had undergone EA-TEF repair in a tertiary referral center. MethodsPreoperative and postoperative records of patients with EA, TEF + EA and isolated EA were examined retrospectively. Accompanied diseases and swallowing dysfunction symptoms were questioned. Bronchoalveolar lavage results were investigated if the patient had flexible bronchoscopy. ResultsA total of 71 children with EA were included in the study, and seven patients who did not have follow-up after surgery were excluded. 46 of the 64 patients continue regular follow-up visits in our department. Male sex, primary EA repair in another center, EA type C, accompanying genetic anomalies, severe tracheomalacia, late per oral feeding (1 year after surgery), and severe GER were found to cause significantly higher incidence of coughing, recurrent wheezing, recurrent pneumonia, and bronchiectasis despite surgical and medical treatments (p = 0.048, p = 0.045, p = 0.009, p = 0.029, p = 0.025). Conclusi̇onEven if anatomical anomalies are corrected by surgery in patients who underwent EA repair, precautions can be taken for GERD, laryngotracheomalacia, and swallowing dysfunction, and effective pulmonary rehabilitation can be initiated with early multidisciplinary approach before the development of respiratory tract symptoms.

A delayed diagnosis of atypical immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome: A case report.

Introduction:Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked (IPEX) syndrome is a rare monogenic autoimmune disease, which is caused by mutations in the forkhead box protein 3 gene, can affect various systems. The typical clinical manifestations of IPEX are enteropathy, type 1 diabetes mellitus, and skin diseases. However, some atypical phenotypes can easily be misdiagnosed clinically.Patient concerns:A 9-year-and-7-month old patient suffered from recurrent wheezing, hematochezia, and eczematous dermatitis at the age of six months, but did not have any manifestations of autoimmune endocrinopathy. The patient was treated with glucocorticoids for more than six years, and he developed bronchiectasis.Diagnosis:Whole exome sequencing revealed a hemizygous pathogenic mutation c.1010G>A, p. (Arg337Gln) in Forkhead box protein 3 gene (NM_014009.3).Interventions:The patient was treated with oral mycophenolate mofetil combined with inhaled budesonide formoterol for six months after diagnosis.Outcomes:The respiratory symptoms of the patient seemed to be controlled but eczematous dermatitis progressed, which led the patient to give up the treatment.Conclusion:Early diagnosis and treatment of IPEX are crucial. Lung injury may be a major problem in the later stages of atypical IPEX, and mycophenolate mofetil seems to control the respiratory symptoms, but could induce significant skin side effects.

Risk factors for recurrent wheezing after bronchiolitis in infants: 2-year follow up in China

BackgroundInfants with bronchiolitis have an increased risk of developing recurrent wheezing and asthma. However, the risk factors for the development of recurrent wheezing after bronchiolitis remains controversial. Our study was to investigate risk factors of post-bronchiolitis recurrent wheezing.MethodsInfants with bronchiolitis were enrolled from November 2016 through March 2017. Nasopharyngeal aspirates were obtained for detection of respiratory viruses which were analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and direct immunofluorescent assay. Serum cytokines including TSLP, IL2, IL13, TIMP-1, MMP-9, IL33, IL5, IL4, IL25, TNF- α and MIP-1α were measured by flow cytometry. Patients were followed up every 3 months for a duration of 2 years by telephone or at outpatient appointments.ResultsWe enrolled 89 infants, of which 81 patients were successfully followed up. In total, 22.2% of patients experienced recurrent wheezing episodes. The proportion of patients with history of eczema, systemic glucocorticoid use and patients with moderate-to-severe disease were significantly higher in the recurrent wheezing group than the non-recurrent wheezing group (83.3% vs 52.4%; 66.7% vs 36.5%; 61.1% vs 33.3%, respectively, all P < 0.05); There were no significant differences between patients with and without recurrent wheezing episodes in the levels of TSLP, IL2, IL13, TIMP-1, MMP-9, IL33, IL5, IL4, IL25, TNF- α and MIP-1α (P > 0.05). Logistic regression analysis showed that history of eczema was an independent risk factor for post-bronchiolitis recurrent wheezing (odds ratio [OR] = 5.622; 95% confidence interval [CI], 1.3–24.9; P = 0.023).ConclusionThe incidence of recurrent wheezing among infants after contracting bronchiolitis was 22.2% during a 2-year follow-up. History of eczema was the only independent risk factor identified and no correlation was found between the specific virus and disease severity in children with post-bronchiolitis recurrent wheezing.

Maternal stress and depression are associated with respiratory phenotypes in urban children

Prenatal and early-life exposure to maternal stress and depression is linked to development of recurrent wheezing in young children. We sought to determine whether maternal stress and depression in early life are associated with nonatopic wheezing phenotype in urban children. The Urban Environment and Childhood Asthma Study examined a birth cohort of children at high risk for asthma in low-income neighborhoods. Prenatal and postnatal (through age 3 years) maternal stress and depression scores were compared with respiratory phenotypes through age 10 years (multinomial regression), self-reported colds (linear regression), and detection of respiratory viruses (Poisson regression). Scores for maternal depression, and, to a lesser extent, maternal perceived stress, were positively related to multiple wheezing phenotypes. In particular, cumulative measures of maternal depression in the first 3 years were related to the moderate-wheeze-low-atopy phenotype (odds ratio, 1.13; [1.05, 1.21]; P< .01). Considering indicators of respiratory health that were used to identify the phenotypes, there were multiple positive associations between early-life scores for maternal stress and depression and increased wheezing illnesses, but no consistent relationships with lung function and some inverse relationships with allergic sensitization. Cumulative maternal stress and depression scores were associated with cumulative number of respiratory illnesses through age 3 years. Among high-risk, urban children, maternal stress and depression in early life were positively associated with respiratory illnesses and a moderate-wheeze-low-atopy phenotype. These results suggest that treating stress and depression in expectant and new mothers could reduce viral respiratory illnesses and recurrent wheeze during the preschool years and some forms of childhood asthma.

Cockroach-induced IL9, IL13, and IL31 expression and the development of allergic asthma in urban children

Cockroach-induced IL9, IL13, and IL31 expression and the development of allergic asthma in urban children

Early life exposure to phthalates and the development of childhood asthma among Canadian children

BackgroundStudies have demonstrated an association between phthalate exposure and childhood asthma, although results have been inconsistent. No epidemiological studies have examined exposure during the first year of life. ObjectiveTo investigate the association between phthalate exposures in the home environment during the first year of life, and subsequent development of childhood asthma and related symptoms. MethodsThis study used a case-cohort design including 436 randomly selected children and all additional cases of asthma at 5 years (ntotal = 129) and recurrent wheeze between 2 and 5 years (ntotal = 332) within the CHILD Cohort Study, a general population Canadian birth cohort of 3455 children. Phthalate exposure was assessed using house dust samples collected during a standardized home visit when children were 3-4 months of age. All children were assessed by specialist clinicians for asthma and allergy at 1, 3 and 5 years. Logistic regression was used to assess the association between exposure to five phthalates and asthma diagnosis at 5 years, and recurrent wheeze between 2 and 5 years, with further stratification by wheeze subtypes (late onset, persistent, transient) based on the timing of onset and persistence of wheeze symptoms. ResultsDi(2-ethylhexyl) phthalate (DEHP) had the highest concentration in dust (mediansubcohort = 217 μg/g), followed by benzyl butyl phthalate (BzBP) (20 μg/g). A nearly four-fold increase in risk of developing asthma was associated with the highest concentration quartile of DEHP (OR = 3.92, 95% CI: 1.87–8.24) including a positive dose-response relationship. A two-fold increase in risk of recurrent wheeze was observed across all quartiles compared to the lowest quartile of DEHP concentrations. Compared to other wheeze subtypes, stronger associations for DEHP were observed with the late onset wheezing subtype, while stronger associations for di-iso-butyl phthalate (DiBP) and BzBP were observed with the transient subtype. DiscussionDEHP exposure at 3-4 months, at concentrations lower than other studies that reported an association, were associated with increased risks of asthma and recurrent wheeze among children at 5 years. These findings suggest the need to assess whether more stringent regulations are required to protect children's health, which can be informed by future work exploring the main sources of DEHP exposure.

Which Wheezing Preschoolers Should be Treated for Asthma?

Wheezing disorders in children younger than 5 years are common, but lack of clarity remains about which children should be treated to prevent symptoms and acute episodes. The aim of this review was to discuss a practical approach to deciding which children younger than 5 years with asthma should be treated, and if so, with which strategy. The importance of having a clear definition of "asthma" for this age group, determined by a collection of presenting respiratory symptoms, without assumptions about underlying mechanisms is addressed. Subsequent consideration should be given to timing, severity, and frequency of symptoms, together with assessment of objective biomarkers, including aeroallergen sensitization and blood eosinophils, to inform whether or not a preschooler with recurrent wheezing requires treatment. Numerous unanswered questions remain about the optimal management of nonallergic preschool wheezing and asthma, and areas of specific unmet need and future directions for research are highlighted.

Dysbiosis in Pediatrics Is Associated with Respiratory Infections: Is There a Place for Bacterial-Derived Products?

Respiratory tract infections (RTIs) are common in childhood because of the physiologic immaturity of the immune system, a microbial community under development in addition to other genetic, physiological, environmental and social factors. RTIs tend to recur and severe lower viral RTIs in early childhood are not uncommon and are associated with increased risk of respiratory disorders later in life, including recurrent wheezing and asthma. Therefore, a better understanding of the main players and mechanisms involved in respiratory morbidity is necessary for a prompt and improved care as well as for primary prevention. The inter-talks between human immune components and microbiota as well as their main functions have been recently unraveled; nevertheless, more is still to be discovered or understood in the above medical conditions. The aim of this review paper is to provide the most up-to-date overview on dysbiosis in pre-school children and its association with RTIs and their complications. The potential role of non-harmful bacterial-derived products, according to the old hygiene hypothesis and the most recent trained-innate immunity concept, will be discussed together with the need of proof-of-concept studies and larger clinical trials with immunological and microbiological endpoints.

Maternal psychiatric status and infant wheezing: The role of maternal hormones and cord blood cytokines.

Maternal psychosocial stress might be associated with development of allergic diseases in the offspring. To evaluate the association of maternal depression and anxiety with ever wheezing and recurrent wheezing among infants and to assess the role of maternal hypothalamo-pituatary-adrenal axis changes and fetal immune response in this association. This study encompasses two designs; cohort design was developed to evaluate the association of prenatal depression with development of wheezing in infants while nested case-control design was used to assess the role of maternal cortisol and tetranectin and cord blood interleukin 13and interferon γ. We enrolled 697 pregnant women. Elementary school graduate mother (odds ratio [OR] = 1.5, p = .06), maternal smoking during pregnancy (OR = 3.4, p = .001), familial history of asthma (OR = 2.7, p < .001) increased the risk of ever wheezing. Elementary school graduate mother (OR = 2.6, p = .002), maternal smoking during pregnancy (OR = 4.8, p < .001) and familial history of asthma (OR = 1.7, p = .01) increased the risk of recurrent wheezing. Maternal previous psychiatric disease, or Edinburgh Postnatal Depression Scale or Spielberger State-Trait Anxiety Inventory scores were not associated with wheezing. Maternal tetranectin levels were significantly higher among never wheezers compared to the ever wheezers (264.3 ± 274.8 vs. 201.6 ± 299.7, p = .04). In conclusion, the major risk factors for ever wheezing and recurrent wheezing were maternal smoking, level of education and family history of asthma. However, maternal depression and anxiety were not determined as risk factors for wheezing. Maternal tetranectin carries potential as a biomarker for wheezing in the infant.

Associated factors with recurrent wheezing in infants: is there difference between the sexes?

ObjectiveIdentify associated factors for recurrent wheezing (RW) in male and female infants. MethodsCross-sectional multicentric study using the standardized questionnaire from the Estudio Internacional sobre Sibilancias en Lactantes (EISL). The questionnaire was applied to parents of 9345 infants aged 12–15 months at the time of immunization/routine visits. ResultsOne thousand two hundred and sixty-one (13.5%) males and nine hundred sixty-three (10.3%) females have had RW (≥3 episodes), respectively (p10 colds episodes (OR = 3.46; IC 95% 2.35–5.07), air pollution (OR = 1.33; IC 95% 1.12–1.59), molds at home (OR = 1.23; IC 95% 1.03–1.47), Afro-descendants (OR = 1.42; IC 95% 1.20–1.69), bronchopneumonia (OR = 1.41; IC; 1.11–1.78), severe episodes of wheezing in the first year (OR = 1.56; IC 95% 1.29–1.89), treatment with bronchodilators (OR = 1.60; IC 95% 1.22–2,1) and treatment with oral corticosteroids (OR = 1,23; IC 95% 0.99–1,52). Associated factors for RW for females were passive smoking (OR = 1.24; IC 95% 1.01−1,51), parents diagnosed with asthma (OR = 1.32; IC 95% 1,08−1,62), parents with allergic rhinitis (OR = 1.26; IC 95% 1.04–1.53), daycare attendance (OR = 1.48; IC 95% 1.17−1,88), colds in the first 6 months of life (OR = 2.19; IC 95% 1.69–2.82), personal diagnosis of asthma (OR = 1.84; IC 95% 1.39–2.44), emergency room visits (OR = 1.78; IC 95% 1.44–2.21), nighttime symptoms (OR = 2.89; IC 95% 2.34–3.53) and updated immunization (OR = 0.62; IC 95% 0.41−0.96). ConclusionThere are differences in associated factors for RW between genders. Identification of these differences could be useful to the approach and management of RW between boys and girls.

Upregulation of neuropeptides and obstructive airway disorder in infancy: A review with focus on post-RSV wheezing and NEHI.

Obstructive airway disorders, common in infancy and early childhood, include some entities that are recognized to have neuro immune mediators as their underlying pathogenetic mechanisms. The best characterized example amongst post-viral wheezing phenotypes is the disorder that follows respiratory syncytial virus (RSV) infection and leads to intermittent, long-term wheezing. The underlying mechanisms of the airway reactivity related to RSV infection have been extensively studies and are associated with dysregulation of the nonadrenergic-noncholinergic (NANC) system, via upregulation of neurotransmitters, typically Substance P. Neuroendocrine hyperplasia of infancy (NEHI), while a less common entity, is a disorder characterized by more severe and long-term obstructive airway disease. NEHI is pathophysiologically characterized by abundance of neuroendocrine cells in the airways containing the neuroimmune mediator bombesin, the release of which is presumed to be the driver of the persistent small airway obstruction and functional air-trapping. Here we review the NANC and neuroendocrine cells, the neurotransmitter systems and their studied roles in pulmonary diseases with a focus on their role in lung development, and subsequent various pediatric lung diseases. We focus on the juxtaposition of the separate neuroimmune mechanisms underlying the pathogenesis of post-RSV recurrent wheezing and NEHI's persistent small airway obstruction. We finally propose a unifying concept of neuropeptides in obstructive disorders that may encompass these two entities and possibly others.