Persistent Wheeze Research Articles

Early-life predictors and risk factors of peanut allergy, and its association with asthma in later-life: Population-based birth cohort study.

BackgroundUnderstanding risk factors for peanut allergy (PA) is essential to develop effective preventive measures.ObjectiveThe objective was to ascertain associates and predictors of PA, and the relationship between PA and asthma severity.MethodsIn a population‐based birth cohort, we investigated the association between objectively confirmed PA with early‐life environmental exposures, filaggrin (FLG)‐loss‐of‐function mutations and other atopic disease. We then examined the association of PA with longitudinal trajectories of sensitization, wheeze and allergic comorbidities, which were previously derived using machine learning. Finally, we ascertained the relationship between PA and asthma severity.ResultsPA was confirmed in 30/959 participants with evaluable data. In the multivariate analysis, eczema in infancy (OR = 4.4, 95% CI 1.5–13.2, p = 0.007), egg sensitization at age 3 years (OR = 9.7, 95% CI 3.3–29.9, p < 0.001) and early‐life cat ownership (OR = 3.0, 95% CI 1.1–8.4, p = 0.04) were independent associates of PA. In the stratified analysis among 700 participants with genetic information, in children with early‐life eczema there was no difference in FLG mutations between children with and without PA (3/18 [16.7%] vs. 42/220 [19.1%], p = 1.00). In contrast, among children without eczema, those with PA were almost eight times more likely to have FLG mutations (2/6 [33.3%] vs. 27/456 [5.9%], p = 0.049). We observed associations between PA and multiple allergic sensitization profiles derived using machine learning, with ~60‐fold increase in risk among individuals assigned to multiple early sensitization. PA was significantly associated with persistent wheeze (but not other wheeze phenotypes), and with trajectories of atopic disease characterized by co‐morbid persistent eczema and wheeze (but not with transient phenotypes). Children with PA were more likely to have asthma, but among asthmatics we found no evidence of an association between PA and asthma severity.ConclusionsPeanut allergy is associated with multiple IgE sensitization and early‐onset persistent eczema and wheeze. FLG loss‐of‐function mutations were associated with peanut allergy in children without eczema.

Epithelial cell responses to rhinovirus identify an early-life-onset asthma phenotype in adults

The study of pathogenic mechanisms in adult asthma is often marred by the lack of precise information about the natural history of the disease. Children who have persistent wheezing during the first 6 years of life and whose symptoms start before age 3 (PW+) are much more likely to have wheezing illnesses due to rhinovirus (RV) in infancy and to have asthma up to adult life than those who do not have persistent wheezing (PW-).To determine if nasal epithelial cells from PW+ adult asthmatics as compared with cells from PW- adult asthmatics show distinct biomechanistic processes activated by RV exposure.

Reassessing the role of tracheobronchomalacia in persistent wheezing.

Tracheobronchomalacia (TBM) is often manifested as wheezing. Reassessing the role of TBM in persistent wheezing in children is essential. We selected children who were diagnosed with TBM by bronchoscopy and who underwent bronchoscopic reexamination for persistent wheezing or chronic cough between January 2009 and July 2019. The clinical and bronchoscopy data were collected and retrospectively reviewed. For statistical analysis, we used the Kaplan-Meier method, Kruskal-Wallis test, and Fisher exact test. A total of 79 patients (57 males and 22 females) were included. The median age of the first TBM diagnosis was 7 (interquartile [IQR] 4-11) months. The median age of the first wheezing episode was 4 (IQR 3-7) months. During the time interval between the two bronchoscopies, malacia lesions resolved in 50 patients (63.3%), improvement was seen in 14 patients (17.7%), no change was observed in 11 patients (13.9%), and the condition was aggravated in 4 patients (5.1%). The malacia lesions in 37 patients resolved before 2 years of age. Among the 50 resolved patients, 22 patients (44.0%) reported wheezing three times or more between bronchoscopy evaluations, and 13 of these 22 patients (59.1%) with atopy or family history of allergic diseases were ultimately diagnosed with bronchial asthma. In children with persistent wheezing, the role of TBM should be reassessed, especially in those with atopy or family history of allergic diseases, and bronchial asthma should be considered early.

Wheeze trajectories: Determinants and outcomes in the CHILD Cohort Study

Wheezing in early life is associated with asthma in adulthood; however, the determinants of wheezing trajectories and their associations with asthma and lung function in childhood remain poorly understood. In the CHILD Cohort Study, we aimed to identify wheezing trajectories and examine the associations between these trajectories, risk factors, and clinical outcomes at age 5 years. Wheeze data were collected at 8 time points from 3 months to 5 years of age. We used group-based trajectory models to derive wheeze trajectories among 3154 children. Associations with risk factors and clinical outcomes were analyzed by weighted regression models. We identified 4 trajectories: a never/infrequent trajectory, transient wheeze, intermediate-onset (preschool) wheeze, and persistent wheeze. Higher body mass index was a common risk factor for all wheeze trajectories compared with that in the never/infrequent group. The unique predictors for specific wheeze trajectories included male sex, lower respiratory tract infections, and day care attendance for transient wheeze; paternal history of asthma, atopic sensitization, and child genetic risk score of asthma for intermediate wheeze; and maternal asthma for persistent wheeze. Blood eosinophil counts were higher in children with the intermediate wheeze trajectory than in those children with the other trajectories at the ages of 1 and 5 years. All wheeze trajectories were associated with decreased lung function and increased risk of asthma at age 5 years. We identified 4 distinct trajectories in children from 3 months to 5 years of age, reflecting different phenotypes of early childhood wheeze. These trajectories were characterized by different biologic and physiologic traits and risk factors.

Lung clearance index predicts persistence of preschool wheeze.

The lung clearance index (LCI) is a measure of pulmonary function. Variable feasibility (50->80%) in preschool children has been reported. There are limited studies exploring its relationship to respiratory symptoms and how it predicts persistent wheeze. We aimed to assess the association with respiratory symptoms in preschool-aged children with LCI and determine its utility in predicting persistent wheeze. LCI was measured in a subcohort of the CHILD Cohort Study at age 3years using SF6 multiple breath washout test mass spectrometry. Respiratory symptom phenotypes at age 3 were derived from children's respiratory symptoms reported by their parents. Responses were used to categorize children into 4symptom groups: recurrent wheeze (3RW), recurrent cough (3RC), infrequent symptoms (IS), and no current symptoms (NCS). At age 5years, these children were seen by a specialist clinician and assessed for persistent wheeze (PW). At age 3years, 69% (234/340) had feasible LCI. Excluding two children with missing data, 232 participants were categorized as follows: 33 (14%) 3RW; 28 (12%) 3RC; 17 (7%) IS; and 154 (66%) NCS. LCI z-score at age 3years was highest in children with 3RW compared to 3RC (mean (SD): 1.14 (1.56) vs. 0.09 (0.95), p<.01), IS (mean (SD): -0.14 (0.59), p<.01), and NCS (mean (SD): -0.08 (1.06), p<.01). LCI z-score at age 3 was predictive of persistent wheeze at age 5 (PW) (AUROC: 0.87). LCI at age 3 was strongly associated with recurrent wheeze at age 3, and predictive of its persistence to age 5.

Air Pollution and Family Related Determinants of Asthma Onset and Persistent Wheezing in Children: Nationwide Case-Control Study

To identify risk factors (air pollution and family related) for the onset of asthma and persistent wheezing in children.All Danish children born from 1997 to 2014 who were managed for asthma onset and persistent wheezing from the age of 1 year to 15 years by using a national registry based, matched case-control design.Children were managed in the Danish National Patient Register for the classification of asthma or persistent wheezing after hospital discharge, or with a minimum of 2 prescriptions for asthma medications. Information regarding concentration of air pollutants (several gases, aerosols, particular matter <2.5µm [PM2.5] and particular matter <10µm), parental asthma diagnoses and asthma medication prescriptions, maternal smoking habits, highest completed parental education, and parental income levels were collected and analyzed for hazard ratios (HRs).From 1997–2014, 3 192 785 children were included in the study, and 122 842 (3.84%) children developed asthma and/or persistent wheezing, with a mean age of development of 1.9 years. Maternal asthma had a higher risk than paternal asthma (adjusted HR): 1.72 (95% CI: 1.72 to 1.77) vs 1.51 (95% CI: 1.48 to 1.53)], but having 2 parents with asthma was associated with a 2.40-fold (2.34-fold to 2.47-fold) risk of childhood asthma. Maternal smoking during pregnancy (adjusted HR: 1.23 [1.18 to 1.28]) or quitting during pregnancy (HR: 1.20 [1.18 to 1.22]) increased the risk of childhood asthma. Exposures to PM2.5, particular matter <10µm, and nitrogen dioxide were also associated with development of asthma, with PM2.5 exposure being the most consistent. Higher parental income levels, together and independently, had a reduced risk for childhood asthma (adjusted HR: 0.85 [95% CI: 0.81 to 0.89) for the highest parental income level, compared with 1.04 (95% CI: 1.00 to 1.08) for the lowest parental income level]. Higher parental education levels, together and independently, had a reduced risk for childhood asthma (adjusted HR: 0.72 [95% CI: 0.69 to 0.75]) for the highest parental education level, compared with 0.98 [95% CI: 0.95 to 1.00] for the lowest parental education level).Parental history of asthma, higher levels of exposure to PM2.5, and maternal smoking during pregnancy all increase a child’s risk of developing asthma and persistent wheezing. High levels of parental educational attainment and income are associated with a lower risk of developing asthma and persistent wheezing in children.Strengths of this study include the use of a large database that covered 18 years. In this study, researchers did not analyze atopy, lung function, or inflammatory markers. A family history of asthma, tobacco exposure and environmental pollutants were confirmed as risk factors for asthma development. Smoking cessation campaigns and environmental strategies to decrease particulate matter exposure may reduce the number of children who develop asthma.

Evaluating the Effect of Vitamin A on Persistent Wheezing in Infants with Bronchiolitis in Southern Iran in 2018

Background: Bronchiolitis is a viral infection that causes the airways (bronchioles) in the lungs to become narrow, which makes breathing difficult. Objectives: This study aimed to evaluate the effect of vitamin A on persistent wheezing in infants with bronchiolitis. Methods: This study was performed on 60 infants with bronchiolitis who were randomly divided into two equal groups (n = 30) of intervention (receiving 5000 units per kg of vitamin A injection) and control. The severity of wheezing and retraction and number of breaths in the patients were recorded. Chi-square, Mann-Whitney U test, and t-test were used to compare the data. Results: Our study showed that 6.7% of infants in the control group had severe wheezing during the discharge, while no wheezing was reported in the intervention group. Also, the rate of moderate wheezing in the control and intervention groups was 40% and 10%, respectively (P = 0.006). Two weeks after treatment, the moderate wheezing frequency in the control group was 30%, but no wheezing was recorded in the intervention group, which was statistically significant (P &lt; 0.001). Conclusions: In this study, administration of vitamin A significantly reduced the severity of wheezing in patients with bronchiolitis. Accordingly, it is recommended that vitamin A along with other treatments, be prescribed for all infants with symptoms of bronchiolitis.

Development of childhood asthma prediction models using machine learning approaches.

Respiratory symptoms are common in early life and often transient. It is difficult to identify in which children these will persist and result in asthma. Machine learning (ML) approaches have the potential for better predictive performance and generalisability over existing childhood asthma prediction models. This study applied ML approaches to predict school-age asthma (age 10) in early life (Childhood Asthma Prediction in Early life, CAPE model) and at preschool age (Childhood Asthma Prediction at Preschool age, CAPP model). Clinical and environmental exposure data was collected from children enrolled in the Isle of Wight Birth Cohort (N=1368, ∼15% asthma prevalence). Recursive Feature Elimination (RFE) identified an optimal subset of features predictive of school-age asthma for each model. Seven state-of-the-art ML classification algorithms were used to develop prognostic models. Training was performed by applying fivefold cross-validation, imputation, and resampling. Predictive performance was evaluated on the test set. Models were further externally validated in the Manchester Asthma and Allergy Study (MAAS) cohort. RFE identified eight and twelve predictors for the CAPE and CAPP models, respectively. Support Vector Machine (SVM) algorithms provided the best performance for both the CAPE (area under the receiver operating characteristic curve, AUC=0.71) and CAPP (AUC=0.82) models. Both models demonstrated good generalisability in MAAS (CAPE 8-year=0.71, 11-year=0.71, CAPP 8-year=0.83, 11-year=0.79) and excellent sensitivity to predict a subgroup of persistent wheezers. Using ML approaches improved upon the predictive performance of existing regression-based models, with good generalisability and ability to rule in asthma and predict persistent wheeze.

Wheezing trajectories from childhood to adulthood in a population-based cohort

BackgroundWheezing may lead to asthma and reduced pulmonary function in later life. The study aims to identify wheezing trajectories and investigate their relation with pulmonary function and asthma-related outcomes at 22 years of age. MethodsIndividuals from a population-based cohort in Brazil (1993 Pelotas Birth Cohort) with post-bronchodilator pulmonary function data at 22 years (3350) were included in the study. From parentally reported (4 and 11 years) and self-reported (15, 18 and 22 years) history of wheezing in the last 12 months, we used a group-based trajectory modelling approach to derive wheezing trajectories. ResultsFour trajectories were identified: never/infrequent, transient-early, late-onset and persistent wheeze. After adjustments, wheezing trajectories remained associated with lower post-bronchodilator values of pulmonary function. Individuals in the persistent wheeze trajectory had a markedly poorer pulmonary function and also showed greater odds of asthma-related outcomes compared to other trajectories groups. Those following this trajectory had on average −109 ml (95% CI: −188; −35), −1.80 percentage points (95% CI: −2.73; −0.87) and −316 ml/s (95% CI: −482; −150) lower FEV1, FEV1/FVC ratio and FEF25–75% respectively; higher odds of self-reported medical diagnosis of allergy (OR 6.18; 95% CI: 3.59; 10.61) and asthma (OR 12.88; 95% CI: 8.91; 18.61) and asthma medication use (OR 9.42; 95% CI: 5.27; 16.87) compared to the never/infrequent group. ConclusionsWheezing trajectories, especially the persistent wheeze trajectory, were related to lower pulmonary function values and increased risk of asthma and allergy diagnosis in early adulthood.

Epidemiology of Adenovirus Pneumonia and Risk Factors for Bronchiolitis Obliterans in Children During an Outbreak in Jilin, China.

Background: Jilin Province, located in northeastern China, recently experienced a human adenovirus (HAdV) epidemic. Few studies involving hospitalized pediatric patients with pneumonia caused by HAdV in our region exist. HAdV pneumonia can lead to severe long-term respiratory sequelae, such as post-infectious bronchiolitis obliterans (PIBO), which has a poor prognosis and greatly influences the quality of life of pediatric patients. However, studies on the risk factors for PIBO are limited.Objective: To describe the HAdV pneumonia prevalence and determine potential risk factors for PIBO development among hospitalized children in Jilin Province, China.Methods: The data of 187 children with HAdV pneumonia (10 months−12 years old) admitted to the First Hospital of Jilin University during an outbreak between October 2018 and January 2020 were retrospectively studied. We analyzed the epidemiological characteristics of HAdV pneumonia, focusing on severe HAdV pneumonia (66 cases). The risk factors for BO development were determined by comparing the demographic and clinical data of the BO and non-BO groups.Results: The largest number of HAdV pneumonia cases occurred in January 2019 (severe n = 18, general n = 21), followed by December 2018 (severe n = 14, general n = 11), June 2019 (general n = 17), July 2019 (general, n = 14), and May 2019 (general, n = 13). In total, 91.98% of the children with HAdV pneumonia were <6 years old (172/187), and 50% of the pediatric patients with severe HAdV pneumonia were <2 years old (33/66). We found that 30.3% of the severe cohort developed BO (20/66), and the strongest independent risk factors for PIBO were persistent wheezing (OR 181.776, 95% CI, 3.385–9,761.543) and acute respiratory failure (OR 51.288, 95% CI, 1.858–1,415.441) during a severe pneumonia episode.Conclusions: The largest number of HAdV pneumonia cases, especially severe cases, occurred in winter in Northeast China, followed by summer. The majority of children admitted with HAdV pneumonia were <6 years old, and half of severe HAdV pneumonia patients were <2 years old. Children who had persistent wheezing or acute respiratory failure during the acute phase of severe HAdV pneumonia were prone to the development of BO.

1031Predictors of Lung function change over the life course: a systematic review

Abstract Background Throughout life, lung function increases, peaks, plateaus and declines. These phases can be influenced by several exposures. Despite the growing body of evidence, the association between these factors and lung function change over the lif course has not been systematically reviewed. Methods Using a pre-defined protocol, two authors independently identified publications related to lung function trajectories and extracted relevant information. We included studies that identified/developed/modelled/reported lung function trajectories based on at least three-time points. Due to heterogeneity in the exposures and methods used to model lung function trajectories, it was not possible to conduct a meta-analysis. Results A total of 12 population-based cohort studies met the inclusion criteria. Of these, 10 were birth cohorts. 4 studies used cluster analysis techniques to develop trajectories while the others used generalized linear interactive modelling. Eight factors were identified, by 2 or more studies, as predictors for reduced lung growth, decline and/or persistently low trajectories. They were low birth weight and parental asthma (n = 2); childhood asthma and allergic sensitization (n = 4); childhood lower respiratory tract infections and childhood persistent wheezing, and environmental tobacco smoke (n = 3); and childhood eczema (n = 2). Conclusions Our review identified risk factors for lung function change that have been consistent at least across two studies. Key messages These findings suggest preventive measures directed at childhood asthma and infections, and tobacco exposure will help promote lung health and prevent unhealthy lung function trajectories.

Follow-up study of airway microbiota in children with persistent wheezing

BackgroundIncreasing evidence revealed that airway microbial dysbiosis was associated with increased risk of asthma, or persistent wheezing (PW). However, the role of lung microbiota in PW or wheezing recurrence remains poorly understood.MethodsIn this prospective observational study, we performed a longitudinal 16S rRNA-based microbiome survey on bronchoalveolar lavage (BAL) samples collected from 35 infants with PW and 28 age-matched infants (control group). A 2-year follow-up study on these PW patients was conducted. The compositions of lower airway microbiota were analyzed at the phylum and genus levels.ResultsOur study showed a clear difference in lower airway microbiota between PW children and the control group. Children with PW had a higher abundance of Elizabethkingia and Rothia, and lower abundance of Fusobacterium compared with the control group. At the end of the 2-year follow-up, 20 children with PW (57.1%) experienced at least one episode of wheezing, and 15 (42.9%) did not suffer from wheezing episodes. Furthermore, PW children with recurrence also had increased abundances of Elizabethkingia and Rothia relative to those who had no recurrence. Additionally, wheezing history, different gender, and caesarean section demonstrated a greater impact in airway microbiota compositions.ConclusionThis study suggests that the alterations of lower airway microbiota could be strongly associated with the development of wheezing, and early airway microbial changes could also be associated with wheezing recurrence later in life.

Changing trends in the prevalence of childhood asthma over 40 years in Greece.

A series of repeated questionnaire surveys among 8- to9-year-old school children in the city of Patras, Greece, demonstrated a continuous rise in the prevalence of wheeze/asthma from 1978 to 2003, with a plateau between 2003 and 2008. We further investigated wheeze/asthma trends within the same environment over the last decade. Two follow-up surveys were conducted in 2013 (N = 2554) and 2018 (N = 2648). Physician-diagnosed wheeze and asthma were analyzed in relation to their occurrence (recent-onset: within the last 2 years; noncurrent: before 2 years; persistent: both prior and within the last 2 years). In 2018, spirometry was also performed in participants reporting symptoms and in a sample of healthy controls. The prevalence of current wheeze/asthma declined from 6.9% in 2008% to 5.2% in 2013% and 4.3% in 2018. The persistent and noncurrent wheeze/asthma groups followed this overall trend (P-for-trend <0.001), while the prevalence of recent-onset wheeze/asthma remained unchanged (P-for-trend >0.05). Persistent and noncurrent wheezers were also more frequently diagnosed with asthma, in contrast to those with recent-onset wheeze. The FEV1 z-score was less than -1 in 32.1% of children with recent-onset and in 22.4% of those with persistent wheeze/asthma; both rates were higher than those of the Noncurrent wheeze/asthma group (7.1%; p < .05) and of healthy controls (3.5%; p < .001). The prevalence of childhood wheeze/asthma has declined significantly during the last decade in Greece. The reversing trend may in part be attributed to changing asthma perceptions among physicians and/or parents, especially in the case of younger children with troublesome respiratory symptoms.

Prevalence and Atopy Association of Mycoplasma Pneumoniae and Chlamydia Pneumoniae Infections in Infants with Recurrent Wheezing

The most common cause in the etiology of wheezing is respiratory tract infections. Viruses (in especially RSV), Chlamydia Pneumoniae and Mycoplasma Pneumoniae bacteria can cause transient airway hypersensitivity and wheezing by causing tissue damage and inflammation when they reach the lower respiratory tract. The association has been demonstrated and discussed between these two atypical bacteria and asthma. By setting major and minor parameters for predicting asthma risk, the asthma predictive index (API) was developed in children with excessive wheezing. This study was planned to examine the relationship of atopy and atypical bacterial infections in infants with persistent wheezing. Thirty-two females and fifty-eight males children under 2 years of age were included in the study. Fifty-six cases (62.2%) were positive for API and thirty-four cases (37.8%) were negative. The presence of infection was investigated by enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) method. It was found that both infections were substantially more serious in the second year than in the first year of life. However no statistically meaningful outcome was obtained, when comparing the presence of both pathogens and API positivity. Regardless of the API, the existence of bacterial agents was found to be statistically meaningful, especially in the range of 1-2 years, when subgroup analysis was performed in children with wheezing under the age of 2 years. It is appropriate to keep in mind the existence of these two bacteria in wheezy children. In the second year of life, both infection agents also showed a statistically significant increase and found that these patients could develop persistent wheezing.

Post-infectious bronchiolitis obliterans in children: Clinical and radiological evaluation and long-term results

Background and objectiveThis study aims to evaluate clinical and radiological findings and treatment outcomes of the patients with PIBO. MethodsOne hundred fourteen children were enrolled. Initial demographic and clinical findings were evaluated. Pre- and post-treatment clinical and radiological findings were compared. ResultsThe median age of the patients at initial pulmonary injury was 7,2 months, the median age at diagnosis was 17.5 months. Persistent wheezing was the most common complaint. Thirty-five patients had mechanical ventilation history. 82,5% of patients had clinical improvement. Bronchiectasis, atelectasis, hyperinflation and air trapping in HRCT improved significantly with treatment. Post-treatment Bhalla scores decreased from 8.3 to 6.5 (p= 0,001). Improvement was observed in radiological and clinical findings after treatment. ConclusionsThis study is one of the largest studies in the literature and one of the few studies that evaluate clinical and radiological outcomes of patients with PIBO.

USE OF LASER PHOTOCOAGULATION THROUGH ENDOBRONCHIAL APPROACH AS AN ALTERNATIVE TREATMENT FOR BRONCHIAL CARCINOID TUMOR.CASE REPORT

Abstract INTRODUCTION Bronchial carcinoid tumor constitutes less than 5% of lung tumors. Eighty-five percent are histologically typical, located in the main airways, generally benign with malignant potential. Clinically they present with persistent cough, respiratory infections and wheezing. Radiologically they manifest as a smooth border mass with calcifications in 25% and obstruction of the main bronchi with atelectasis. The definitive diagnosis is histopathological. According to current NCCN guidelines resection is the first line of treatment. MATERIAL AND METHODS Female, 37 years old, smoker, presents with dyspnea, dry cough and fever. Hypoxemia with absent VM in the left lung base. Chest RX/CT with increased density in LIL and hypercapillary nodule of 15x14mm in LMB that conditions stenosis of the lumen and atelectasis of the LSL. No adenopathies. Spirometry FVC 43% FEV1 44% FEV1/FVC 82%. Video/ecobronchoscopy with endobronchial lesion in LMB occupying 100% of the lumen cT1cN0.PA: carcinoid tumor. RESULTS In MDT, endobronchial approach with rigid bronchoscopy is decided, performing mechanical debridement in its entirety and laser photocoagulation with immediate bronchial repermeabilization. Spirometry FVC 67%; FEV1 66%; FEV1/FVC 98%. PA: typical carcinoid. Follow-up for 12 months with CT and bronchoscopy without evidence of recurrence. CONCLUSION According to Reuling, the endobronchial approach is a treatment alternative in intraluminal tumors &amp;lt;20 mm, regardless of their histologic grade; likewise, Van der Heijden proposes it as the first line of therapy; however, more prospective studies with long-term follow-up are needed. Follow-up with CT and bronchoscopy is recommended to rule out local recurrences.

Asthma, bronchial hyperresponsiveness, allergy and lung function development until early adulthood: A systematic literature review.

BackgroundIt is unclear in which periods of life lung function deficits develop, and whether these are affected by risk factors such as asthma, bronchial hyper‐responsiveness (BHR) and allergic comorbidity. The goal of this systematic review was to identify temporal associations of asthma, BHR and allergic comorbidity with large and small lung function development from birth until peak function in early adulthood.MethodsWe searched MEDLINE, EMBASE, Web of Science and CINAHL for papers published before 01.01.2020 on risk factors and lung function measurements of large and small airways. Studies were required to report lung function at any time point or interval from birth until peak lung function (age 21‐26) and include at least one candidate risk factor.ResultsOf the 45 papers identified, 44 investigated cohorts and one was a clinical trial with follow‐up. Asthma, wheezing, BHR and allergic sensitization early in life and to multiple allergens were associated with a lower lung function growth of large and small airways during early childhood compared with the control populations. Lung function development after childhood in subjects with asthma or persistent wheeze, although continuing to grow at a lower level, largely tracked parallel to non‐affected individuals until peak function was attained.Clinical implications and future researchDeficits in lung function growth develop in early childhood, and children with asthma, BHR and early‐life IgE (poly)sensitization are at risk. This period is possibly a critical window of opportunity to identify at‐risk subjects and provide treatment aimed at preventing long‐term sequelae of lung function.

Childhood wheezing phenotypes and their association to perinatal factors: a longitudinal study.

Multiple gestational and early life factors have been described as the variables that increase the risk for each phenotype of infantile wheezing. Our objective was to study the evolution of wheezing in a cohort of children followed up to 9-10 years of age and its relationship with different perinatal risk factors. A longitudinal study was made on the evolution of wheezing, over time, in 1164 children from Salamanca (Spain) included in the International Study of Wheezing in Infants, when the children were 12 months old. They were classified into three phenotypes: transient early wheezing (last episode before 3 years of age), early persistent wheezing (start before 3 years age and persisting thereafter), and late-onset wheezing (first episode after 3 years of age). Univariate and multivariable analyses were performed to establish associations between the different phenotypes and perinatal factors. Data were obtained corresponding to a total of 531 children. Of these, 169 (31.8%) had experienced transient early wheezing, 100 (18.8%) early persistent wheezing, 28 (5.3%) late-onset wheezing, and 234 (44.1%) had never experienced wheezing. Cesarean delivery, early exposure to infections, the presence of atopic eczema, and a smoking father were associated with transient early wheezing. Early persistent wheezing was associated with a family history of allergy, smoking, and obstetric diseases. Exclusive breastfeeding was identified as a protective factor in both transient and persistent early wheezing. Late-onset wheezing was associated with the male gender and with maternal history of rhinitis and eczema. Wheezing phenotypes were associated with different risk perinatal factors. Knowledge in the field is essential in order to influence the modifiable factors.

Effects of the COVID-19 pandemic and lockdown on symptom control in preschool children with recurrent wheezing.

IntroductionPreschool wheezers are at high risk of recurrent attacks triggered by respiratory viruses, sometimes exacerbated by exposure to allergens and pollution. Because of the COVID‐19 infection, the lockdown was introduced, but the effects on preschool wheezers are unknown. We hypothesized that there would be an improvement in outcomes during the lockdown, and these would be lost when the lockdown was eased.Materials and MethodsPatients underwent medical visits before and after the COVID‐19 lockdown. We recorded the childhood Asthma Control Test (cACT) and a clinical questionnaire. Data on symptoms, the need for medications and the use of healthcare resources were recorded. We compared these data with retrospective reports from the preceding year and prospectively acquired questionnaires after lockdown.ResultsWe studied 85 preschool wheezers, mean age 4.9 years. During the lockdown, cACT score was significantly higher (median 25 vs. 23); families reported a dramatic drop in wheezing episodes (51 vs. none), significant reductions in the day and nighttime symptoms, including episodes of shortness of breath (p < .0001); the use of salbutamol and oral corticosteroids (OCS) dropped significantly (p < .0001) and 79 (95%) patients needed no OCS bursts during the lockdown. Finally, patients had significantly fewer extra medical examinations, as well as fewer Emergency Room visits (p < .0001). All were improved compared with the same time period from the previous year, but outcomes worsened significantly again after lockdown (cACT median: 22).ConclusionsDuring the national lockdown, children with persistent preschool wheeze showed a significant clinical improvement with reduction of respiratory symptoms, medication use for exacerbations, and use of healthcare resources. This trend reversed when lockdown restrictions were eased.

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.