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Introduction: Severe bronchiolitis (i.e., bronchiolitis requiring hospitalization) is linked to childhood asthma development. Despite a growing understanding of risk factors for developing post-bronchiolitis asthma, protective factors remain unclear. In this study, we aimed to investigate whether exposure to residential greenness between birth and bronchiolitis hospitalization is associated with asthma and atopic asthma development by age 6 years., Methods: We analyzed a US severe bronchiolitis cohort from hospitalization to age 6 years, investigating how the normalized difference vegetation index (NDVI) and chlorophyll index green (CI green), measured in small (100 m) and large (500 m) radiuses around homes, relate to asthma and atopic asthma by age 6 years. We also explored whether maternal antibiotic use, daycare attendance, and respiratory virus type during hospitalization act as effect modifiers., Results: The study cohort included 861 infants, with 239 (28%) developing asthma by age 6 years-152 atopic, 17 nonatopic, and 70 unclassified. Early life residential exposure to high NDVI and CI green levels was associated with lower odds of asthma (OR Adj for NDVI within a 100 m radius, 0.18; 95% CI, 0.05-0.78; and OR Adj for CI green levels within a 100 m radius, 0.53; 95% CI, 0.31-0.90). Associations also were significant for the development of atopic asthma (OR Adj 0.16; 95% CI, 0.03-0.96; and OR Adj 0.46; 95% CI, 0.25-0.92; respectively). Results were similar for the 500 m radius exposures. No effect modification was noted., Conclusion: In a U.S. bronchiolitis cohort, exposure to residential greenness between birth and bronchiolitis hospitalization is linked to lower asthma and atopic asthma risk by age 6 years., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Therapy with immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of metastatic melanoma but is also associated with various immune-related adverse events (AE), including pulmonary toxicity. Herein, we describe the case of a 60-year-old female with metastasized melanoma with BRAF mutation under combination immunotherapy with ipilimumab and nivolumab, who presented with a persistent, nonproductive cough for the last two months. Her CT-scan showed de novo bronchial inflammation and wall thickening in all lung fields. Initial treatment with antimicrobial treatment and inhalation corticosteroids did not resolve her symptoms, nor the radiologic abnormalities. Additional testing with transbronchial cryobiopsy showed a histologic picture of diffuse ill-formed granulomas and the presence of moderate chronic active inflammation of the respiratory epithelium, consistent with medication-related bronchiolitis. Bronchiolitis, as present in this case, has rarely been reported as an immune-related AE. A thorough diagnostic workup is mandatory as it remains a diagnosis of exclusion. Management consists of discontinuing ICIs and administering systemic corticosteroids. The addition of immunosuppressive agents (e, infliximab, cyclophosphamide, or mycophenolate mofetil) can be considered in refractory cases. In our case, clinical and radiologic resolution was achieved after discontinuing the ICI and treatment with high-dose prednisone. This case shows that although bronchiolitis is a rare immune-related side effect of ICIs, oncologists, and pulmonologists should always be aware of this relatively easily treatable AE., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Myasthenia gravis (MG) is the most common paraneoplastic disorder associated with thymic neoplasms. MG can develop after thymectomy, and this condition is referred to post-thymectomy myasthenia gravis (PTMG). Diffuse panbronchiolitis (DPB), is a rare form of bronchiolitis and is largely restricted to East Asia, has been reported in association with thymic neoplasms. Only three cases of combined MG and DPB have been reported in the literature., Case Presentation: A 45-year-old Taiwanese woman presented to our hospital with productive cough, rhinorrhea, anosmia, ear fullness, shortness of breath, and weight loss. She had a history of thymoma, and she underwent thymectomy with adjuvant radiotherapy 7 years ago. Chest computed tomography scan revealed diffuse bronchitis and bronchiolitis. DPB was confirmed after video-assisted thoracoscopic surgery lung biopsy, and repeated sputum cultures grew Pseudomonas aeruginosa. She has been on long-term oral azithromycin therapy thereafter. Intravenous antipseudomonal antibiotics, inhaled amikacin, as well as oral levofloxacin were administered. Three months after DPB diagnosis, she developed ptosis, muscle weakness, and hypercapnia requiring the use of noninvasive positive pressure ventilation. MG was diagnosed based on the acetylcholine receptor antibody and repetitive stimulation test results. Her muscle weakness gradually improved after pyridostigmine and corticosteroid therapies. Oral corticosteroids could be tapered off ten months after the diagnosis of MG. She is currently maintained on azithromycin, pyridostigmine, and inhaled amikacin therapies, with intravenous antibiotics administered occasionally during hospitalizations for respiratory infections., Conclusions: To our knowledge, this might be the first case report of sequential development of DPB followed by PTMG. The coexistence of these two disorders poses a therapeutic challenge for balancing infection control for DPB and immunosuppressant therapies for MG., (© 2024. The Author(s).)

This case-control study aimed to investigate the association between short-term (1 to 5 days) and medium-term (31 days) exposure to air pollutants (PM 2.5 , PM 10 , BC, NO 2 ) at home/daycare and the risk of 'severe bronchiolitis' (defined as 'requiring hospitalization for bronchiolitis') in children under 2 years in Antwerp, Belgium. We included 118 cases and 79 controls admitted to three general hospitals from October 2020 to June 2021. Exposure levels were predicted using an interpolation model based on fixed measuring stations. We used unconditional logistic regression analysis to assess associations, with adjustment for potential confounders. There were hardly any significant differences in the day-to-day air pollution values between cases and controls. Medium-term (31 days) exposure to PM 2.5 , PM 10 , and NO 2 was however significantly higher in cases than controls in univariate analysis. Logistic regression revealed an association between severe bronchiolitis and interquartile range (IQR) increases of PM 2.5 and PM 10 at home and in daycare, as well as IQR increases of NO 2 in daycare. Controls were however overrepresented in low pollution periods. Time-adjustment reduced the odds ratios significantly at home for PM 2.5 and PM 10 (aOR 1.54, 95%CI 0.51-4.65; and 2.69, 95%CI 0.94-7.69 respectively), and in daycare for. PM 2.5 (aOR 2.43, 95%CI 0.58-10.1). However, the association between severe bronchiolitis and medium-term air pollution was retained in daycare for IQR increases of PM 10 (aOR 5.13, 95%CI 1.24-21.28) and NO 2 (aOR 3.88, 95%CI 1.56-9.61) in the time-adjusted model .   Conclusion: This study suggests a possible link between severe bronchiolitis and medium-term (31 days) air pollution exposure (PM 10 and NO 2 ), particularly in daycare. Larger studies are warranted to confirm these findings. What is Known: • Bronchiolitis is a leading cause of hospitalization in infants globally and causes a yearly seasonal wave of admissions in paediatric departments worldwide. • Existing studies, mainly from the USA, show heterogeneous outcomes regarding the association between air pollution and bronchiolitis. What is New: • There is a possible link between severe bronchiolitis and medium-term (31 days) air pollution exposure (PM10 and NO2), particularly in daycare. • Larger studies are needed to validate these trends., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Severe bronchiolitis (i.e., bronchiolitis requiring hospitalization) during infancy is a heterogeneous condition associated with a high risk of developing childhood asthma. Yet, the exact mechanisms underlying the bronchiolitis-asthma link remain uncertain. Birth cohort studies have reported this association at the population level, including only small groups of patients with a history of bronchiolitis, and have attempted to identify the underlying biological mechanisms. Although this evidence has provided valuable insights, there are still unanswered questions regarding severe bronchiolitis-asthma pathogenesis. Recently, a few bronchiolitis cohort studies have attempted to answer these questions by applying unbiased analytical approaches to biological data. These cohort studies have identified novel bronchiolitis subtypes (i.e., endotypes) at high risk for asthma development, representing essential and enlightening evidence. For example, one distinct severe respiratory syncytial virus (RSV) bronchiolitis endotype is characterized by the presence of Moraxella catarrhalis and Streptococcus pneumoniae, higher levels of type I/II IFN expression, and changes in carbohydrate metabolism in nasal airway samples, and is associated with a high risk for childhood asthma development. Although these findings hold significance for the design of future studies that focus on childhood asthma prevention, they require validation. However, this scoping review puts the above findings into clinical context and emphasizes the significance of future research in this area aiming to offer new bronchiolitis treatments and contribute to asthma prevention., (Copyright © 2024 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: Bronchiolitis is the leading cause of hospitalization in children under one year of age, with annual epidemics. Since the onset of the SARS-CoV-2 coronavirus disease pandemic (COVID-19), there has been a change in the transmission of other respiratory viruses. Our aim in this paper was to describe how COVID-19 had affected the distribution of acute bronchiolitis in our country., Methods: We conducted a retrospective descriptive study of the cases of bronchiolitis treated in a sample of Spanish hospitals belonging to four autonomous communities. A chi-square test and Student's t- test were used to compare epidemiological and demographic variables between patients attending the hospital with bronchiolitis during January 2021-June 2021 with patients attending the hospital in the previous three years (2018-2020)., Results: We analyzed 6,124 cases of bronchiolitis (58.8% males and 41.2% females). The mean age was 0.5 years (SD: 0.4). In 2020, we observed a decrease of bronchiolitis cases compared to 2019 of 67%. During 2020 and 2021, the epidemic season started in January-February and peaked in June. During the first half of 2021, the highest percentage of admissions for bronchiolitis associated with RSV infection was observed in hospitals in central Spain corresponding to the Autonomous Community of Madrid (78.5% of admissions)., Conclusions: The COVID-19 pandemic significantly modifies the seasonality of bronchiolitis. In our country, the flow and distribution of the disease are not uniform. It starts in the center of Spain and ends on the coast.

Background: Outdoor air pollution is supposed to influence the course of bronchiolitis, but the evidence is limited. The present study aimed at evaluating the role of outdoor air pollutants on hospitalization for bronchiolitis., Methods: Infants aged ≤12 months referred for bronchiolitis to our Pediatric Emergency Department in Bologna, Italy, from 1 October 2011 to 16 March 2020 (nine epidemic seasons) were retrospectively included. Daily concentrations of benzene (C 6 H 6 ), nitrogen dioxide (NO 2 ), particulate matter ≤2.5 μm (PM 2.5 ), and ≤10 μm (PM 10 ), and the mean values of individual patient exposure in the week and the 4 weeks before hospital access were calculated. The association between air pollutants exposure and hospitalization was evaluated through logistic regression analysis., Results: A total of 2902 patients were enrolled (59.9% males; 38.7% hospitalized). Exposure to PM 2.5 in the 4 weeks preceding bronchiolitis was identified as the main parameter significantly driving the risk of hospitalization (odds ratio [95% confidence interval]: 1.055 [1.010-1.102]). After stratifying by season, higher values of other outdoor air pollutants were found to significantly affect hospitalization: 4-week exposure to C 6 H 6 (Season 2011-2012, 4.090 [1.184-14.130]) and PM 2.5 (Season 2017-2018, 1.282 [1.032-1.593]), and 1-week exposure to C 6 H 6 (Season 2012-2013, 6.193 [1.552-24.710]), NO 2 (Season 2013-2014, 1.064 [1.009-1.122]), PM 2.5 (Season 2013-2014, 1.080 [1.023-1.141]), and PM 10 (Season 2018-2019, 1.102 [0.991-1.225])., Conclusion: High levels of PM 2.5 , C 6 H 6 , NO 2 , and PM 10 may increase the risk of hospitalization in children affected by bronchiolitis. Open-air exposure of infants during rush hours and in the most polluted areas should be avoided., (© 2023 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Background: Bronchiolitis is a leading cause of infant hospitalization. Recent research suggests the heterogeneity within bronchiolitis and the relationship of airway viruses and bacteria with bronchiolitis severity. However, little is known about the pathobiological role of fungi. We aimed to identify bronchiolitis mycotypes by integrating fungus and virus data, and determine their association with bronchiolitis severity and biological characteristics., Methods: In a multicentre prospective cohort study of 398 infants (age <1 year, male 59%) hospitalized for bronchiolitis, we applied clustering approaches to identify mycotypes by integrating nasopharyngeal fungus (detected in RNA-sequencing data) and virus data (respiratory syncytial virus [RSV], rhinovirus [RV]) at hospitalization. We examined their association with bronchiolitis severity-defined by positive pressure ventilation (PPV) use and biological characteristics by nasopharyngeal metatranscriptome and transcriptome data., Results: In infants hospitalized for bronchiolitis, we identified four mycotypes: A) fungi M.restricta virus RSV/RV , B) fungi M.restricta virus RSV , C) fungi M.globosa virus RSV/RV , D) fungi not-detected virus RSV/RV mycotypes. Compared to mycotype A infants (the largest subtype, n = 211), mycotype C infants (n = 85) had a significantly lower risk of PPV use (7% vs. 1%, adjOR, 0.21; 95% CI, 0.02-0.90; p = 0.033), while the risk of PPV use was not significantly different in mycotype B or D. In the metatranscriptome and transcriptome data, mycotype C had similar bacterial composition and microbial functions yet dysregulated pathways (e.g., Fc γ receptor-mediated phagocytosis pathway and chemokine signaling pathway; FDR <0.05)., Interpretation: In this multicentre cohort, fungus-virus clustering identified distinct mycotypes of infant bronchiolitis with differential severity risks and unique biological characteristics., Funding: This study was supported by the National Institutes of Health., Competing Interests: Declaration of interests All authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Smoking-related interstitial lung diseases (ILDs) are a group of heterogeneous, diffuse pulmonary parenchymal disease processes associated with tobacco exposure. These disorders include pulmonary Langerhans cell histiocytosis, respiratory bronchiolitis-associated ILD, desquamative interstitial pneumonia, acute eosinophilic pneumonia, and combined pulmonary fibrosis and emphysema. This review summarizes the current evidence of pathogenesis, clinical manifestations, diagnostic approach, prognosis, and treatment modalities for these diseases. We also discuss the interstitial lung abnormalities incidentally detected in radiologic studies and smoking-related fibrosis identified on lung biopsies., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Patients with pulmonary graft-versus-host disease (pGVHD) have a poor prognosis after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Furthermore, pGVHD pathogenesis is not fully elucidated in humans, and currently available immunosuppressants are inadequately effective. We performed pathologic evaluation of lung specimens from 45 allo-HSCT recipients with pGVHD who underwent lung transplantation. Patient pathology was characterized by bronchiolitis and subpleural perivascular inflammation, with B-cell, monocyte, and T-cell accumulation around bronchioles. Bronchiolitis, perivascular inflammation, and peribronchial macrophage aggregation were also identified in a murine pGVHD model after transplant of bone marrow cells and splenocytes from C57BL/6 to B10.BR mice. Among mitogen-activated protein kinase kinase (MEK) inhibitors, cobimetinib, but not trametinib, improved survival rates. Cobimetinib attenuated bronchiolitis, improved airway resistance and lung compliance in the mice, and suppressed activation of B cells and tumor necrosis factor α production by monocytes in vitro; these features were not suppressed by trametinib or tacrolimus. Furthermore, cobimetinib suppressed activation of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling, resulting in B-cell and monocyte suppression. Dual inhibition of the MEK/extracellular signal-regulated kinase (ERK) and PI3K/AKT pathways using a combination of trametinib and the PI3K inhibitor taselisib strongly suppressed B-cell activation in vitro and improved mouse survival rates compared with vehicle or monotherapy with trametinib or taselisib. Imaging mass cytometry of human pGVHD revealed that T cells around bronchioles were positive for phosphorylated ERK, whereas B cells were positive for phosphorylated AKT. Thus, perivascular inflammation and bronchiolitis mediated by activation of the MEK/ERK and PI3K/AKT pathways are essential for pGVHD and represent a potential novel therapeutic target in humans., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Objective: Pulmonary Langerhans cell histiocytosis is a cystic lung disease characterized by the proliferation of parenchymal dendritic cells. The disease can become chronic or even cause pulmonary fibrosis. Our aim in this study was to investigate the typical histological findings and interstitial fibrosis in pulmonary Langerhans cell histiocytosis cases., Material and Method: In the study, cases that had undergone diagnostic resection were screened. Smoking, histological stage (subacute, subacute-chronic), and cystic and eosinophilic granulomas were confirmed in the cases. In addition to emphysema, chronic nonspecific bronchiolitis, interstitial fibrosis (subpleural-paraseptal fibrosis, peribronchial fibrosis, fibrotic nonspecific interstitial pneumonia), honeycomb-type fibrocysts, and unexpected lesions were investigated. Descriptive and comparative (Fisher exact test) statistical analyses were used in the study (p < 0.05)., Results: A total of 27 cases were detected; age distribution was 17-68 (36.4). Smoking was present in 15 (55.5%) cases. Six (22.2%) cases were subacute, and 21 (7.7%) cases were subacute-chronic histological stage. A cystic lesion was present in 22 (81.4%) cases. All cases had emphysema accompanying the underlying lesions. Chronic nonspecific bronchiolitis was detected in 14 (51.8%) cases. Interstitial fibrosis was detected in 8 (29.6%) patients. Compared to interstitial fibrosis and nonfibrosis, there was no significant difference between being younger than 39 years, gender, smoking, and histological stage (p=0.41; 1; 0.69; 0.63, respectively)., Conclusion: There is a risk of developing interstitial fibrosis patterns and honeycomb-type fibrocysts in the progression of pulmonary Langerhans cell histiocytosis. Histopathological evaluation can play an important role in the detection of risk groups.

The results of several clinical trials suggest that continuous positive airway pressure (CPAP) for acute bronchiolitis can be more effective than high-flow nasal cannula (HFNC). The use of HFNC involved a minimum reduction (5%) in admissions to the pediatric intensive care unit (PICU) in our hospital. Our main aim was to evaluate its safety and effectiveness as respiratory support for patients with bronchiolitis in a pediatric general ward. A secondary goal was to compare the admissions to PICU and the invasive mechanical ventilation (IMV) rate of patients treated with HFNC and those treated with HFNC/b-CPAP during the 2018-2019 and 2019-2020 epidemic seasons, respectively. Two prospective single-centre observational studies were performed. For the main aim, a cohort study (CS1) was carried out from 1st of November 2019 to 15th of January 2020. Inclusion criteria were children aged up to 3 months with bronchiolitis treated with b-CPAP support when HFNC failed. Epidemiological and clinical parameters were collected before and 60 min after the onset of CPAP and compared between the responder (R) and non-responders (NR) groups. NR was the group that required PICU admission. One hundred fifty-eight patients were admitted to the ward with bronchiolitis and HFNC. Fifty-seven out of one hundred fifty-eight required b-CPAP. No adverse events were observed. Thirty-two out of fifty-seven remained in the general ward (R-group), and 25/57 were admitted to PICU (NR-group). There were statistically significant differences in respiratory rate (RR) and heart rate (HR) between both groups before and after the initiation of b-CPAP, but the multivariable models showed that the main differences were observed after 60 min of therapy (lower HR, RR, BROSJOD score and FiO2 in the R-group). For the secondary aim, another cohort study (CS2) was performed comparing data from a pre-b-CPAP bronchiolitis season (1st of November 2018 to 15th January 2019) and the b-CPAP season (2019-2020). Inclusion criteria in pre-b-CPAP season were children aged up to 3 months admitted to the same general ward with moderate-severe bronchiolitis and with HFNC support. Admissions to PICU during the CPAP season were significantly reduced, without entailing an increase in the rate of IMV., Conclusion: The implementation of b-CPAP for patients with bronchiolitis in a pediatric ward, in whom HFNC fails, is safe and effective and results in a reduction in PICU admissions., What Is Known: • Bronchiolitis is one of the most frequent respiratory infections in children and one of the leading causes of hospitalization in infants. • Several studies suggest that the use of continuous positive airway pressure (CPAP) for acute bronchiolitis can be more effective than the high flow nasal cannula (HFNC). CPAP is a non-invasive ventilation (NIV) therapy used in patients admitted to pediatric intensive care unit (PICU) with progressive moderate-severe bronchiolitis. There is little experience in the literature on the use of continuous positive airway pressure (CPAP) for acute bronchiolitis in a general ward., What Is New: • CPAP could be safely and effectively used as respiratory support in young infants with moderate-severe bronchiolitis in a general ward and it reduced the rate of patients who required PICU admission. • Patients' heart and respiratory rate and their FiO2 needs in the first 60 minutes may help to decide whether or not to continue the CPAP therapy in a general ward., (© 2022. The Author(s).)

Objectives: to analyze the climate seasonality of respiratory diseases in children aged 0-9 years and present a model to predict hospital admissions for 2021 to 2022., Methods: verify, in a temporal manner, the correlation of admissions for pneumonia, bronchitis/bronchiolitis, and asthma with meteorological variables, aiming to demonstrate seasonality with the adjustment of temporal series models., Results: there was a seasonal effect in the number of registered cases for all diseases, with the highest incidence of registrations in the months of autumn and winter., Conclusions: it was possible to observe a tendency towards a decrease in the registration of pneumonia cases; In cases of admissions due to bronchitis and bronchiolitis, there was a slight tendency towards an increase; and, in occurrence rates of asthma, there was no variation in the number of cases.

Studies have associated the human respiratory syncytial virus which causes seasonal childhood acute bronchitis and bronchiolitis (CABs) with climate change and air pollution. We investigated this association using the insurance claims data of 3,965,560 children aged ≤ 12 years from Taiwan from 2006−2016. The monthly average incident CABs increased with increasing PM2.5 levels and exhibited an inverse association with temperature. The incidence was 1.6-fold greater in January than in July (13.7/100 versus 8.81/100), declined during winter breaks (February) and summer breaks (June−August). The highest incidence was 698 cases/day at <20 °C with PM2.5 > 37.0 μg/m3, with an adjusted relative risk (aRR) of 1.01 (95% confidence interval [CI] = 0.97−1.04) compared to 568 cases/day at <20 °C with PM2.5 < 15.0 μg/m3 (reference). The incidence at ≥30 °C decreased to 536 cases/day (aRR = 0.95, 95% CI = 0.85−1.06) with PM2.5 > 37.0 μg/m3 and decreased further to 392 cases/day (aRR = 0.61, 95% CI = 0.58−0.65) when PM2.5 was <15.0 μg/m3. In conclusion, CABs infections in children were associated with lowered ambient temperatures and elevated PM2.5 concentrations, and the high PM2.5 levels coincided with low temperature levels. The role of temperature should be considered in the studies of association between PM2.5 and CABs.

Introduction: Viral bronchiolitis is a common lower respiratory tract infection in infants. Environmental and genetic factors can favor respiratory tract infections., Aim: The aim of this study is to analyze risk factors for bronchiolitis and to investigate the predisposing factors for developing transient wheezing and asthma through a 6-year follow-up after hospitalization for bronchiolitis compared with a group of healthy controls that belonged to Piccolipiù cohort, who never had bronchiolitis., Methods: We enrolled 645 infants hospitalized with bronchiolitis. A structured questionnaire was used to obtain demographic and clinical data. At 6 years of age, 370 cases and 183 controls were investigated for the presence of asthma by the structured questionnaire, for prick test and for spirometry, and were classified to asthmatic, transient wheezing, and no wheezing/no asthma., Results: Breastfeeding was an independent protective factor (odds ratio [OR]: 0.3, 95% confidence interval [95% CI]: 0.2-0.4, p < 0.001) and tobacco smoke was a risk factor for the development of bronchiolitis (OR: 2.1, 95% CI: 1.4-3.1, p < 0.001). Analyzing follow-up, bronchiolitis increased the risk of developing transient wheezing by 12.9 (95% CI: 6.3-26.1, p < 0.001) and of developing asthma by 4.6 (95% CI: 1.9-10.7, p < 0.001). A positive family history of atopy increased the risk of developing asthma by 3.1 (95% CI: 1.4-6.7, p = 0.005). Asthmatic patients had a lower % FEV1, a lower % flow-volume curve (FVC), and a lower FEV1/FVC value, and they had more frequently positive skin prick test., Conclusion: Bronchiolitis is influenced by environmental factors: tobacco smoke increases its risk and breastfeeding is a protective factor. At the end of 6 years of follow-up, bronchiolitis is a significant risk factor to have pre-school wheezing and asthma., (© 2021 Wiley Periodicals LLC.)

Background: Diffuse panbronchiolitis is a chronic airway disease characterized by diffuse inflammation of respiratory bronchioles and peribronchial tissue. We present a case of diffuse panbronchiolitis developed after lung transplantation, which to our knowledge has not been previously described in the literature., Case Report: A 52-year-old white woman was admitted with reports of weakness, shortness of breath, and productive cough 6 months after bilateral sequential lung transplantation. Thorax computed tomography revealed the appearance of a budding branch pattern in the lower lobes of both lungs. Repeated transbronchial lung biopsies were not diagnostic. A lower lobe wedge biopsy with thoracotomy was performed in the patient, whose respiratory function gradually deteriorated. Dense lymphocyte infiltration in the respiratory bronchiole wall and foamy macrophage groups in the adjacent interstitial area were detected in the histopathologic sections. The dramatic response was achieved with pulse steroid therapy in a short time. Rapidly worsening clinical course and response to the pulse steroid therapy suggested acute cellular rejection., Conclusions: Acute cellular rejection is expected within the first year in lung transplant recipients. Diffuse panbronchiolitis may be a kind of clinical presentation in lung recipients and should be considered in patients who develop severe graft function loss in a short time., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Respiratory Syncytial Virus (RSV) induced bronchiolitis is a common lung infection and a major cause of infant hospitalization and mortality. Unfortunately, there is no known cure for RSV but several vaccines are in various stages of clinical trials. Currently, immunoprophylaxis is a preventative measure consisting of a series of monthly shots that should be administered at the start, and throughout, peak RSV season. Thus, the successful implementation of immunoprophylaxis is contingent upon understanding when outbreak seasons will begin, peak, and end. In this research we estimate the seasonal epidemic curves of RSV induced bronchiolitis using a spatially varying change point model. Further, in a novel approach and using the fitted change point model, we develop a historical matching algorithm to generate real time predictions of seasonal curves for future years., (Copyright © 2021. Published by Elsevier Ltd.)

The aim of this study was to investigate the effect of tobacco smoke exposure among severely pediatric ICU patients. A prospective epidemiological observational study was conducted among children with bronchiolitis younger than 2 years of age admitted to the Pediatric Intensive Care Unit of Children's University Hospital La Paz during the October 2017 to March 2018 outbreak. On admission, parents were asked whether they smoked. In children who required invasive mechanical ventilation, endotracheal aspirate was collected at the time of intubation. A total of 102 patients with bronchiolitis were studied. Among these, 14 (47%) of 30 infants whose parents smoked required invasive mechanical ventilation vs. 14 (19%) of 72 whose parents were nonsmokers (p = 0.007). Among patients on invasive mechanical ventilation, 10 (71%) of 14 infants with secondhand smoke exposure presented pulmonary bacterial superinfection vs. 3 (21%) of 14 in the unexposed (p = 0.012).Conclusion: Secondhand smoke exposure is an additional high risk for pulmonary bacterial superinfection and invasive mechanical ventilation in infants with severe acute bronchiolitis What is known: •Environmental tobacco smoke exposure is known to be an important risk factor for childhood lower respiratory tract infections. •Tobacco smoke makes structural changes in the respiratory tract and reduces the immune response. What in new: •Secondhand smoke exposure showed to be associated with the increased need and duration of invasive mechanical ventilation, and pediatric intensive care length of stay. •Tobacco smoke exposure is an additional risk factor for the presence of bacteria in the endotracheal aspirate., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Seven species of coronavirus cause acute respiratory illness in humans. Coronavirus HKU 1 (CoV HKU 1) was first described in 2005 in an adult patient with pneumonia in Hong Kong. Although it is a well-known respiratory tract pathogen, there is not much information about its role in hospitalized adults, especially in southern Europe. Here, we describe a case of radiologically demonstrated CoV HKU 1-related bronchiolitis with acute respiratory failure in an adult female without significant comorbidities except obesity.

Background: Child exposure to cigarette smoke is harmful. It should be reduced through parental smoking cessation interventions. The aim of our study was to determine the impact of simple advice provided by the pediatrician on the smoking habits of parents of children with cystic fibrosis (CF), diabetes mellitus (DM), and infants hospitalized for bronchiolitis., Methods: Parents were interviewed on their smoking habits. Smoking cessation advice was provided by the pediatrician. A new smoking habits assessment was done at 3 months by phone interviews., Results: A total of 260 parents were interviewed (91 in the CF group, 136 in the DM group, and 33 in the bronchiolitis group). A total of 70 parents were active smokers: 33% of parents of children with CF, 23.5% of parents of children with DM, and 24.2% for those with infants hospitalized for bronchiolitis (p = .42). In the CF group, smoking cessation had been significantly more frequently discussed with the medical team previously. A total of 67 smoking parents (95.7%) answered the 3-month assessment: 29.8% reported having started a smoking cessation process; 10.4% had quit smoking. The quitting rate was significantly higher in the groups of patients followed for a respiratory disorder (37.5% for bronchiolitis, 15% for CF vs. 0% for DM, p = .005)., Conclusion: This study shows the important role that information and simple advice from pediatricians can have in initiating smoking cessation in parents of patients followed in specialized clinics or who are hospitalized, with a greater efficiency in parents of patients suffering from lung disorders., (© 2021 Wiley Periodicals LLC.)

Introduction: Environmental exposure to tobacco increases the risk of respiratory disease in infants. However, the impact of maternal smoking on the development of acute bronchiolitis has hardly been assessed. The aim of this study was to determine the incidence of acute bronchiolitis and to analyse the effect of prenatal and postnatal maternal smoking on the development of this disease., Patients and Methods: A prospective, observational study was performed on healthy newborns from a third level hospital born between October 2015 and February 2016. Questionnaires were completed by the mothers at discharge from maternity and followed-up for two years. These collected information about prenatal and postnatal smoking, lifestyle, family and personal history, and the development of bronchiolitis. A bivariate and multivariate logistic regression analysis was performed., Results: A total of 223 newborns were included, of whom 13.9% were exposed to tobacco smoking during gestation, 21.4% in the postnatal period, and 12.4% in both times. The incidence of bronchiolitis was 28.7% at one year of life, and 34.5% at two years. The multivariate analysis demonstrated that the prenatal and postnatal exposure to tobacco is an independent risk factor for the development of bronchiolitis (OR 4.38; 95% CI; 1.63-11.76), while prolonged breastfeeding is a protective factor (OR 0.13; 95% CI; 0.04-0.48). Other factors that were statistically significant were: atopic dermatitis (OR 2.91; 95% CI; 1.26-6.73), and gestational age (OR 1.42; 95% CI; 1.08-1.88)., Conclusions: Children exposed to prenatal and postnatal maternal smoking have a higher risk of suffering bronchiolitis. Reducing the smoking habit in women that intend to become pregnant must be a priority in preventive medicine., (Copyright © 2021 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

In addition to chronic obstructive pulmonary disease (COPD) and bronchogenic carcinoma, smoking can also cause interstitial lung diseases (ILDs) such as respiratory bronchiolitis (RB), RB with ILD (RB-ILD), desquamative interstitial pneumonia (DIP), Langerhans cell granulomatosis (LCG) and idiopathic pulmonary fibrosis-usual interstitial pneumonia (IPF-UIP). However, smoking seems to have a protective effect against hypersensitivity pneumonitis (HP), sarcoidosis and organising pneumonia (OP). High-resolution computed tomography (HRCT) has a pivotal role in the differential diagnosis. RB is extremely frequent in smokers, and is considered a marker for smoking exposure. It has no clinical relevance in itself since most patients with RB are asymptomatic. It is frequent to observe the association of RB with other smoking-related diseases, such as LCG or pulmonary neoplasms. In RB-ILD, HRCT features are more conspicuous and diffuse than in RB, but there is no definite cut-off between the two entities and any distinction can only be made by integrating imaging and clinical data. RB, RB-ILD and DIP may represent different degrees of the same pathological process, consisting in a bronchiolar and alveolar inflammatory reaction to smoking. Smoking is also a well-known risk factor for pulmonary fibrosis. Multidisciplinary discussion and follow-up can generally solve even the most difficult cases.

Seasonal variations in UV-B radiation may influence vitamin D status, and this, in turn, may influence the risk of bronchiolitis hospitalization. The aim of this study was using a causal inference approach to investigate, simultaneously, the interrelationships between personal and environmental risk factors at birth/hospital admission (RFBH), serum vitamin D levels and bronchiolitis hospitalization. A total of 63 children (<2 years old) hospitalized for bronchiolitis (34 RSV-positive) and 63 controls were consecutively enrolled (2014-2016). Vitamin D levels and some RFBH (birth season, birth weight, gestational age, gender, age, weight, hospitalization season) were recorded. The discovered RFBH effects on the risk ok bronchiolitis hospitalization were decomposed into direct and vitamin-D mediated ones through Mediation Analysis. Winter-spring season (vs. summer-autumn) was significantly associated with lower vitamin D levels (mean difference -11.14 nmol/L). Increasing serum vitamin D levels were significantly associated with a lower risk of bronchiolitis hospitalization (OR = 0.84 for a 10-nmol/L increase). Winter-spring season and gestational age (one-week increase) were significantly and directly associated with bronchiolitis hospitalization (OR = 6.37 and OR = 0.78 respectively), while vitamin D-mediated effects were negligible (1.21 and 1.02 respectively). Using a comprehensive causal approach may enhance the understanding of the complex interrelationships among RFBH, vitamin D and bronchiolitis hospitalization.

Although nearly 3,000 e-cigarette-related hospitalizations have been reported in North America, the long-term outcomes in these patients have not been described. We followed an 18-year-old boy who survived acute critical illness and respiratory failure related to 5 months of e-cigarette use. Chronic irreversible airflow obstruction and markedly abnormal 129 Xe MRI ventilation heterogeneity was observed and persisted 8 months after hospital discharge, despite improvement in quality-of-life and chest CT findings. Lung clearance index and oscillometry measures were also highly abnormal at 8 months postdischarge. Although 129 Xe MRI ventilation abnormalities were dominant in the lung apices and central lung regions, the pattern of ventilation defects was dissimilar to ventilation heterogeneity observed in patients with obstructive lung disease, such as asthma and COPD. Our findings underscore the long-term functional impacts of e-cigarette-related lung injury in survivors of critical illness; longitudinal evaluations may shed light on the pathophysiologic mechanisms that drive e-cigarette-related lung disease., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Bronchiolitis manifests as a variety of histological features that explain the complex clinical profiles and imaging aspects. In the period between January 2011 and June 2015, patients with a cryobiopsy diagnosis of bronchiolitis were retrospectively retrieved from the database of our institution. Clinical profiles, imaging features and histologic diagnoses were analysed to identify the role of cryobiopsy in the diagnostic process. Twenty-three patients with a multidisciplinary diagnosis of small airway disease were retrieved (14 females, 9 males; age range 31-74 years old; mean age 54.2 years old). The final MDT diagnoses were post-infectious bronchiolitis (n = 5), constrictive bronchiolitis (n = 3), DIPNECH (n = 1), idiopathic follicular bronchiolitis (n = 3), Sjogren's disease (n = 1), GLILD (n = 1), smoking-related interstitial lung disease (n = 6), sarcoid with granulomatous bronchiolar disorder (n = 1), and subacute hypersensitivity pneumonitis (n = 2). Complications reported after the cryobiopsy procedure consisted of two cases of pneumothorax soon after the biopsy (8.7%), which were successfully managed with the insertion of a chest tube. Transbronchial cryobiopsy represents a robust and mini-invasive method in the characterization of small airway diseases, allowing a low percentage of complications and good diagnostic confidence.

The type-2 inflammatory response that promotes asthma pathophysiology occurs in the absence of sufficient immunoregulation. Impaired regulatory T cell (Treg) function also predisposes to severe viral bronchiolitis in infancy, a major risk factor for asthma. Hence, we hypothesized that long-lived, aberrantly programmed Tregs causally link viral bronchiolitis with later asthma. Here we found that transient plasmacytoid dendritic cell (pDC) depletion during viral infection in early-life, which causes the expansion of aberrant Tregs, predisposes to allergen-induced or virus-induced asthma in later-life, and is associated with altered airway epithelial cell (AEC) responses and the expansion of impaired, long-lived Tregs. Critically, the adoptive transfer of aberrant Tregs (unlike healthy Tregs) to asthma-susceptible mice failed to prevent the development of viral-induced or allergen-induced asthma. Lack of protection was associated with increased airway epithelial cytoplasmic-HMGB1 (high-mobility group box 1), a pro-type-2 inflammatory alarmin, and granulocytic inflammation. Aberrant Tregs expressed lower levels of CD39, an ectonucleotidase that hydrolyzes extracellular ATP, a known inducer of alarmin release. Using cultured mouse AECs, we identify that healthy Tregs suppress allergen-induced HMGB1 translocation whereas this ability is markedly impaired in aberrant Tregs. Thus, defective Treg programming in infancy has durable consequences that underlie the association between bronchiolitis and subsequent asthma.

Purpose: Stereotactic body radiation therapy is a therapeutic option offered to high surgical risk patients with lung cancer. Focal lung irradiation in mice is a new preclinical model to help understand the development of lung damage in this context. Here we developed a mouse model of lung stereotactic therapy using arc delivery and monitored the development of lung damage while varying the beam size and dose delivered., Methods and Materials: C57BL/6JRj mice were exposed to 90 Gy focal irradiation on the left lung using 1-mm diameter, 3 × 3 mm 2 , 7 × 7 mm 2 , or 10 × 10 mm 2 beam collimation for beam size effect and using 3 × 3 mm 2 beam collimation delivering 20 to 120 Gy for dose effect. Long-term lung damage was monitored with micro-computed tomography imaging with anatomopathologic and gene expression measurements in the injured patch and the ipsilateral and contralateral lungs., Results: Both 1-mm diameter and 3 × 3 mm 2 beam collimation allow long-term studies, but only 3-mm beam collimation generates lung fibrosis when delivering 90 Gy. Dose-effect studies with constant 3-mm beam collimation revealed a dose of 60 Gy as the minimum to obtain lung fibrosis 6 months postexposure. Lung fibrosis development was associated with club cell depletion and increased type II pneumocyte numbers. Lung injury developed with ipsilateral and contralateral consequences such as parenchymal thickening and gene expression modifications., Conclusions: Arc therapy allows long-term studies and dose escalation without lethality. In our dose-delivery conditions, dose-effect studies revealed that 3 × 3 mm 2 beam collimation to a minimum single dose of 60 Gy enables preclinical models for the assessment of lung injury within a 6-month period. This model of lung tissue fibrosis in a time length compatible with mouse life span may offer good prospects for future mechanistic studies., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Competing Interests: None

Background: Obliterative bronchiolitis (OB) is a known issue during minor histocompatibility antigen (mHA) disparity during lung transplantation. This study evaluated gene expression in a murine orthotropic lung transplantation model using microarray analysis., Methods: Left lungs from C57BL/10(H-2b) donor mice were transplanted into mHA-mismatched C57BL/6(H-2b) recipient mice. Three groups (OB, non-OB, and sham controls) were confirmed pathologically and analyzed. Gene expression changes in the lung grafts were determined by microarray and immunohistochemical staining, and genes were verified by quantitative PCR in the lungs and mediastinal lymph nodes (LNs)., Results: A total of 1343 genes were upregulated in the OB lungs compared to the sham group. Significant upregulation was observed for genes related to innate, e.g. Tlr2 and CCL3 and adaptive immunity, e.g. H2-ab1 and Il-21. Positive labeling for MHC class II antigen was observed in the bronchial epithelium of OB accompanied with B cells. We found increased Tlr2, Ccl3, H2-ab1, Il-21, Ighg3, Ifng, and Pdcd1 mRNA expression in the OB lung, and increased Il-21, Ighg3, and Pdcd1 expression in the OB LNs., Conclusions: Adaptive and innate immune reactions were involved in OB after lung transplantation, and genetic examination of related genes could be used for detection of OB., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: TN reports personal fees from AstraZeneca, personal fees from Olympus, outside the submitted work; AK reports grants from Japan Agency for Medical Research and Development, grants from Japan Society for the Promotion of Science, grants from SRL Inc., grants from SCRUM Inc., outside the submitted work; IY reports grants from TAIHO PHARMA, grants from Pfizer, grants from Boehringer Ingelheim, grants from SHIONOGI & CO, outside the submitted work. The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Introduction : Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory tract infections in infancy. While many infants are infected with RSV, the nature and severity of the disease vary among individuals. RSV causes bronchiolitis, pneumonia, and asthma exacerbation. However, most children infected with RSV have only mild upper airways disease and may be asymptomatic. Areas covered : Despite efforts to elucidate mechanisms for the various clinical responses to RSV infection, they remain largely unknown, suggesting that susceptibility and disease are influenced by multiple intrinsic and extrinsic factors. This article reviews the available literature on the field of RSV disease severity and discusses important factors associated to susceptibility and different disease outcome. Expert opinion : The severity of RSV-induced illness is a phenomenon that depends on a variety of graded mechanisms of interaction between the host, virus, and environment. This may lead to differences in the intensity of immune response in the lung and different courses of the disease. By characterizing, classifying, and grading the affecting factors in high-risk patients versus those who do not fall ill by RSV, we may find therapies or point to disease-limiting medications.

Three major histologic patterns of bronchiolitis: obliterative bronchiolitis, follicular bronchiolitis, and diffuse panbronchiolitis, are reviewed in detail. These distinct patterns of primary bronchiolar injury provide a useful starting point for formulating a differential diagnosis and considering possible causes. In support of the aim toward a cause-based classification system of small airway disease, a simple diagnostic algorithm is provided for further subclassification of the above 3 bronchiolitis patterns according to the major associated etiologic subgroups., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Pulmonary manifestations of inflammatory bowel disease are increasingly recognized in patients with ulcerative colitis and Crohn's disease. Most commonly, incidental abnormalities are noted on chest imaging or pulmonary function tests. Although clinically significant pulmonary disease is less common, it can carry significant morbidity for patients. We review the presenting symptoms, workup, and management for several of the more common forms of inflammatory bowel disease-related pulmonary disease. Increased awareness of the spectrum of extraintestinal inflammatory bowel disease will help providers more readily recognize this phenomenon in their own patients and more comprehensively address the protean sequelae of inflammatory bowel disease., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The frequency of bacteremia in children hospitalized due to respiratory syncytial virus infection (RSV) rarely exceeds 1%, but a recent study reported a 10% risk of bacteremia. In this study, we set out to verify the frequency, usefulness, and costs of blood cultures in RSV infections. We addressed the issue by reviewing medical files of 512 children, aged 8 days-121 months, who were hospitalized during January 2010 and June 2017. The RSV-related diagnoses included bronchiolitis (390 patients), RSV pneumonia (65 patients), and bronchitis (57 patients). There were 212 blood cultures performed in 185 patients (36%). In 10 cultures (5.4%), the following pathogens were identified: Staphylococcus haemolyticus, 4; Staphylococcus epidermidis, 1; Staphylococcus hominis, 1; Corynebacterium, 1 Streptococcus parasanguinis, 1; Rothia mucilaginosa, 1; Micrococcus luteus, 1; and Streptococcus hominis, 1 case. However, all of these pathogens were identified as a contamination of samples only. Therefore, both positive blood cultures turned out in fact negative, and the patients having either result of blood culturing showed no clinically relevant differences. The total cost of blood cultures in the pediatric ward amounted to €1980. If performed in each and every patient, the costs would have reached €5490. In conclusion, the frank frequency of bacteremia in children with RSV infection, with no sepsis, seems exceedingly low, which confirms the earlier findings. Thus, blood culturing, generating high costs, is of negligible clinical value. The study provides no evidence supporting a routine blood culture in case of children hospitalized due to RSV infection.

Background: A cluster of severe lung disease occurred at a manufacturing facility making industrial machines. We aimed to describe disease features and workplace exposures., Methods: Clinical, functional, radiologic, and histopathologic features were characterized. Airborne concentrations of thoracic aerosol, metalworking fluid, endotoxin, metals, and volatile organic compounds were measured. Facility airflow was assessed using tracer gas. Process fluids were examined using culture, polymerase chain reaction, and 16S ribosomal RNA sequencing., Results: Five previously healthy male never-smokers, ages 27 to 50, developed chest symptoms from 1995 to 2012 while working in the facility's production areas. Patients had an insidious onset of cough, wheeze, and exertional dyspnea; airflow obstruction (mean FEV 1  = 44% predicted) and reduced diffusing capacity (mean = 53% predicted); and radiologic centrilobular emphysema. Lung tissue demonstrated a unique pattern of bronchiolitis and alveolar ductitis with B-cell follicles lacking germinal centers, and significant emphysema for never-smokers. All had chronic dyspnea, three had a progressive functional decline, and one underwent lung transplantation. Patients reported no unusual nonoccupational exposures. No cases were identified among nonproduction workers or in the community. Endotoxin concentrations were elevated in two air samples; otherwise, exposures were below occupational limits. Air flowed from areas where machining occurred to other production areas. Metalworking fluid primarily grew Pseudomonas pseudoalcaligenes and lacked mycobacterial DNA, but 16S analysis revealed more complex bacterial communities., Conclusion: This cluster indicates a previously unrecognized occupational lung disease of yet uncertain etiology that should be considered in manufacturing workers (particularly never-smokers) with airflow obstruction and centrilobular emphysema. Investigation of additional cases in other settings could clarify the cause and guide prevention., (© 2019 Wiley Periodicals, Inc.)

Objective: To evaluate trends and geographic distribution of infant bronchiolitis hospitalizations in Chile, a country with large variation in solar radiation (SR) and high rates of urban air pollution., Methods: We performed a nationwide ecological study of bronchiolitis hospitalizations from 2001 to 2014. We investigated the associations of regional SR (a proxy of vitamin D status) and regional fine particulate matter (PM2.5) air pollution with bronchiolitis hospitalizations. We also evaluated the role of sociodemographic factors, including regional poverty, education, indigenous population, and rurality rates., Results: During the study period, 119 479 infants were hospitalized for bronchiolitis in Chile; 59% were boys. The mean bronchiolitis hospitalization rate increased from 29 to 41 per 1000 infants per year (P = .02). There was an inverse correlation between regional SR and incidence of hospital admissions for bronchiolitis (r = -0.52, P = .049), accounting for 27% of these hospitalizations. There was also a significant direct correlation between regional ambient PM2.5 and bronchiolitis hospitalizations (R = 0.68, P = .006), accounting for 42% of the variation in admission rate. High firewood and/or coal residential use for heating, high regional poverty, lower years of education, and high rurality rates were also significantly correlated with bronchiolitis hospitalization rates. None of the environmental or sociodemographic factors evaluated were correlated with regional case fatality rates or length of stay at the hospital., Conclusions: This ecological study revealed significant associations between regional SR, air pollution, and sociodemographic factors with infant bronchiolitis hospitalizations in Chile, suggesting that these factors play a major role in the incidence and severity of respiratory infections in early childhood., (© 2019 Wiley Periodicals, Inc.)

Little is known about respiratory morbidity and asthma risk in preterm infants (PTIs) with a gestational age (GA) over 32 weeks. This was a prospective study carried out from birth to 7-8 years, comparing two groups: (a) PTIs (GAs 32 weeks + 1 day to 35 weeks + 0 days, without comorbidities) and (b) full-term infants (FTIs; GA ≥ 37 weeks). Risk and protective factors for bronchiolitis and asthma were identified. A total of 232 children (116/group) were included. Sixty-six (56.9%) PTIs and 43 (37.1%) FTIs presented bronchiolitis (p = 0.002). Recurrent wheezing was 52 (44.8%) on PTIs versus 36 (31.0%) on FTIs (p = 0.03). Asthma at school aged was 27 (23.3%) on PTIs and 8 (6.9%) on FTIs (p = 0.020). Asthma risk factors were only detected in group A.Conclusion: PTIs had a higher prevalence of bronchiolitis, recurrent wheezing and asthma; risk factors for asthma are the following: older siblings, allergic father, atopic dermatitis and antibiotic treatment in the first 3 years of life and prematurity itself, which also acted as protective factor for atopic dermatitis. What is known: • In recent decades, there has been a significant increase in the birth of premature babies and consequently, also in the pathologies secondary to the prematurity: a greater number of complications and disorders related to the development and maturation of many organs and systems, especially the respiratory system. Several studies, especially in full-term infants and very preterm infants, have tried to elucidate the risk factors that may influence the development of persistent or chronic respiratory problems such asasthma, but little is known about the aetiology of these disorders in the late or moderate preterm infants. Inthis group of children, the role played by certain factors (early use of antibiotics, chorioamnionitis, smokeexposure, paternal asthma, etc.) on late respiratory morbidity, or asthma, is inconclusive. • Moderate-to-late preterm infants are more predisposed to developing recurrent wheezing/asthma and should adopt control measures. What is new: • Our work provides data related to little-understood aspects of respiratory diseases in this group of late or moderate preterm infants (gestational age between 32 weeks plus 1 day and 35 weeks plus 0 days), by monitoring their evolution from birth to 7-8 years of age, compared with another group of full-term newborns. We aimed to establish the prevalence of bronchiolitis and recurrent wheezing in these children during their first years of life. • The prevalence of school-aged asthma and the risk factors for contracting it were also investigated.

This Perspectives in Veterinary Medicine article seeks to define, describe putative causes, and discuss key diagnostic tests for primary and secondary bronchiolar disorders to propose a classification scheme in cats with support from a literature review and case examples. The small airways (bronchioles with inner diameters <2 mm), located at the transitional zone between larger conducting airways and the pulmonary acinus, have been overlooked as major contributors to clinical syndromes of respiratory disease in cats. Because the trigger for many bronchiolar disorders is environmental and humans live in a shared environment with similar susceptibility, understanding these diseases in pet cats has relevance to One Health. Thoracic radiography, the major imaging modality used in the diagnostic evaluation of respiratory disease in cats, has low utility in detection of bronchiolar disease. Computed tomography (CT) with paired inspiratory and expiratory scans can detect pathology centered on small airways. In humans, treatment of bronchiolar disorders is not well established because of heterogeneous presentations and often late definitive diagnosis. A review of the human and veterinary medical literature will serve as the basis for a proposed classification scheme in cats. A case series of cats with CT or histopathologic evidence of bronchiolar lesions or both, either as a primary disorder or secondary to extension from large airway disease or interstitial lung disease, will be presented. Future multi-institutional and multidisciplinary discussions among clinicians, radiologists, and pathologists will help refine and develop this classification scheme to promote early and specific recognition and optimize treatment., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Serious bacterial infections in young infants with bronchiolitis are rare. Febrile infants <1 month old with bronchiolitis often receive a lumbar puncture (LP), despite limited data for this practice and lack of clinical practice guidelines for this population. The primary objective was to investigate practice patterns in performance of LPs in the ED management of febrile infants aged ≤30 days with bronchiolitis., Methods: A cross-sectional survey of two national paediatric emergency research networks (PediatricEmergency Research Canada (PERC) and the PediatricEmergency Research UK/Ireland (PERUKI)) was conducted January to November 2017 using a modified Dillman technique. The survey was preceded by a clinical vignette describing a well appearing, 21-day-old infant with low-grade fever, respiratory findings typical of bronchiolitis and no perinatal serious bacterial infection (SBI) risk features., Results: The response rate from PERC was 169/250 (68%) and 172/201 (86%) from PERUKI. Nine physicians in training were excluded, leaving 332 eligible participants. Although most physicians believe that neonates with bronchiolitis rarely have meningitis (PERC 141/161 (87.6%); PERUKI 154/171 (90%)) and feel comfortable diagnosing bronchiolitis in this group (PERC 136/161 (84.5%); PERUKI 143/171 (83.6%)), there was significant variation in the proportion who would be likely/very likely to perform an LP (PERC 100/161 (62.1%); PERUKI 15/171 (8.8%)) (p<0.0001). Practice in Canada, <10 years in practice and lack of comfort with diagnosing bronchiolitis represent multivariable predictors of LP; OR 23.7 (95% CI 11.7 to 47.9), 2.3 (95% CI 1.2 to 4.2) and 2.5 (95% CI 1.1 to 5.0), respectively. Rapid knowledge of respiratory syncytial virus positivity would decrease LP probability from 35.4% to 20.2%., Conclusion: Estimated probability of performing LPs and other interventions in otherwise healthy febrile neonates with bronchiolitis is highly variable between emergency physicians in Canada and the UK/Ireland. Network, <10 years in ED practice and comfort level with diagnosing bronchiolitis in newborns constitute independent predictors of the likelihood of LP performance., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There have been no reports on the relationship between lung radiological patterns and rheumatoid arthritis (RA) disease activity or RA treatment response in patients with RA-associated lung disease (RA-LD)., Methods: Patients with RA-LD who underwent treatment for RA from April 2005 to March 2015 were retrospectively evaluated. RA-LD patients were divided into three groups based on high-resolution computed tomography (HRCT) patterns [usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), and bronchiolitis]. The disease activity score of 28 joints-erythrocyte sedimentation rate (DAS28-ESR) and the response of RA to treatment, as measured by the European League Against Rheumatism (EULAR) response criteria, were investigated., Results: A total of 77 patients (21 with UIP, 23 with NSIP, and 33 with bronchiolitis) were enrolled. Median scores (interquartile range) on the DAS28-ESR at baseline were 5.27 (4.76-5.74), 5.48 (4.24-6.34), and 5.04 (3.90-5.66) for UIP, NSIP, and bronchiolitis, respectively; there were no statistical differences between the three groups (p = 0.412). One year after baseline, 19 (90%), 14 (61%), and 19 (58%) of patients in the UIP, NSIP, and bronchiolitis groups, respectively, were considered good or moderate responders, as evaluated using the EULAR response criteria; there was a significant difference between these three groups (p = 0.014). Multiple logistic regression analysis revealed that the UIP pattern was significantly associated with good or moderate response to RA treatment 1 year after baseline (p = 0.012)., Conclusions: These results suggest that NSIP and bronchiolitis HRCT patterns may be risk factors for resistance to RA therapy., (Copyright © 2019 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Yellow nail syndrome (YNS) is a rare clinical syndrome characterized by a triad of yellow thick nail, lymphedema and respiratory diseases. We experienced 2 cases of YNS with diffuse panbronchiolitis (DPB)-like pulmonary manifestation. Since YNS might be hidden to those who have been diagnosed with DPB, physicians should be alert to recognize nail signs of YNS in case of DPB refractory to macrolide therapy. We hereby review previous case reports of YNS and discuss its pulmonary manifestations.

Introduction: The prevalence and the variability of clinical practice in acute bronchiolitis make it a perfect candidate to monitor the proper use of resources. The aim of this study is to analyse the differences in the use of non-recommended resources in the management of bronchiolitis in the Emergency Department, before and after the establishment of a new protocol., Methods: A retrospective study was conducted on a sample of patients diagnosed with acute bronchiolitis in the Emergency Department of a tertiary hospital, before (December 2014) and after (December 2016) the implementation of a new protocol. A comparison was made on the use of diagnostic tests and treatments in both groups., Results: The analysis included a total of 113 patients with acute bronchiolitis examined in December 2014, and 128 patients in December 2016. The clinical characteristics in both groups were similar. In the post-protocol period, there was a significant decrease in the use of salbutamol, both in the Emergency Department (33.6% vs 19.5%, P<.01) and at discharge (46.7% vs 15.2%, P<.001); adrenaline (12.4% vs 2.4%, P=.002), and nebulised hypertonic saline solution (5.3% vs 0.8%, P=.04). Rapid respiratory syncytial virus (RSV) testing was also decreased (40.7% vs 26.6%, P=.01). This decrease was not associated with an increase in the number of admissions or re-assessments in the Emergency Department., Conclusions: The establishment of a new protocol for acute bronchiolitis decreased the use of non-recommended resources, mainly the use of bronchodilators and rapid RSV testing., (Copyright © 2017 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

Current data indicate that the "bronchiolitis" diagnosis comprises more than one condition. Clinically, pathophysiologically, and even genetically three main clusters of patients can be identified among children suffering from severe bronchiolitis (or first wheezing episode): (a) respiratory syncytial virus (RSV)-induced bronchiolitis, characterized by young age of the patient, mechanical obstruction of the airways due to mucus and cell debris, and increased risk of recurrent wheezing. For this illness, an effective prophylactic RSV-specific monoclonal antibody is available; (b) rhinovirus-induced wheezing, associated with atopic predisposition of the patient and high risk of subsequent asthma development, which may, however, be reversed with systemic corticosteroids in those with severe illness; and (c) wheeze due to other viruses, characteristically likely to be less frequent and severe. Clinically, it is important to distinguish between these partially overlapping patient groups as they are likely to respond to different treatments. It appears that the first episode of severe bronchiolitis in under 2-year-old children is a critical event and an important opportunity for designing secondary prevention strategies for asthma. As data have shown bronchiolitis cannot simply be diagnosed using a certain cutoff age, but instead, as we suggest, using the viral etiology as the differentiating factor., (© 2018 The Authors. Allergy Published by John Wiley & Sons Ltd.)

Objective: Respiratory syncytial virus (RSV) is a common pathogen during infancy, with the potential to cause serious disease and mortality in high-risk groups. The objective of this study was to characterize trends of RSV and bronchiolitis hospitalizations in the first year in a population-based cohort and assess differences in trends according to risk status., Methods: Using an observational retrospective cohort design, we examined a California population-based dataset of vital statistics linked to hospital discharge data for up to 1 year after birth from 1997-2011. Infants were categorized by medical condition and then by gestational age. Medical conditions of interest included chronic lung disease, certain congenital heart diseases, or others known to affect risk for developing severe bronchiolitis. The primary outcome was hospitalization due to RSV; secondary outcome was hospitalization for unspecified bronchiolitis (UB) not coded as RSV. Annual person-year rates were calculated for infants <12 months of age during January to December of each year., Results: Of 7,298,401 infants born during the study period, 121,230 (1.7%) had a medical condition associated with risk; these infants experienced 6853 RSV and 6568 UB hospitalizations in the first year. In infants without medical conditions, 96,694 RSV and 69,886 UB hospitalizations occurred. All-cause infant hospitalizations declined over time from 12.2 to 9.3 per 100 person-years. RSV hospitalization rates for infants with medical conditions decreased from 7.6 to 3.4 per 100 person-years, with the largest relative decline in infants with chronic lung disease (12.0 to 5.0 per 100 person-years). For infants without medical conditions, RSV hospitalizations declined from 1.4 to 0.8 per 100 person-years, with greater decreases among preterm infants with earlier gestational age. UB hospitalization rates remained relatively stable across the study years, from 6.2 to 5.4 and 1.0 to 0.8 per 100 person-years for infants with and without medical conditions., Conclusions: Various interventions may have contributed to observed decreases in RSV hospitalizations from 1998-2011, which were greater in high-risk populations recommended for RSV immunoprophylaxis and not observed with UB. Further efforts to promote evidence-based practice and optimal targeting of appropriate interventions will ensure continued improvement in care for vulnerable infants., Competing Interests: This study was supported by AstraZeneca (Gaithersburg, MD). KM and CSA are employed by AstraZeneca. HL received funding from AstraZeneca for research effort and travel expenses to present findings at a national conference. MB received research funding from AstraZeneca. There are no patents, products in development, or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Smoking-related lung diseases traverse a spectrum of clinicopathologic entities, with cases often comprising a complex mixture of findings. The complexity of the diagnostic process extends beyond the histologic findings to the nomenclature, which is murky from a seemingly unending expansion of terms being applied to a handful of pathologic changes. Here, we focus our review on smoking-related interstitial fibrosis, respiratory bronchiolitis, and desquamative interstitial pneumonia, 3 entities that perhaps show the most histologic overlap and suffer from competing terminology.

Pneumonia is the leading cause of morbidity and mortality in children less than 5 years of age in developing countries like Bangladesh. Although WHO guideline classified severe pneumonia by symptoms and signs of the patients, radiological and laboratory investigations were not studied well. There was increasing number of cases of bronchiolitis which meet the criteria of WHO classified severe pneumonia are reported. The objective of the study was to assess the clinical and radiological parameters of severe pneumonia in 2 months to 59 months hospitalized children according to WHO guideline. This cross sectional study was conducted in pediatrics department of Mymensingh Medical College Hospital, Mymensingh, Bangladesh from July, 2015 to December 2015. Total 150 patients were included in this cross sectional study according to their clinical symptoms. Firstly, the chest x-ray was done in all the patients and radiographs were reviewed by an expert radiologist who was blind about the cases. Then the patients were classified as pneumonia and bronchiolitis according to the clinical features and radiology findings. Majority of the patients 83(55.3%) were between 2-6 months of age and mean age was 7.52±8.87. Maximum 105(70%) patients were male and 45(30%) were female. Most of them 70(47%) came from low middle class family. Regarding clinical features, all patients 150 had cough and chest indrawing. Ronchi found in 135(90%) patients, difficult breathing and fast breathing found in 130(87%) patients, crepitation in 122(81%) patients, wheeze in 93(62%) patients, dull on percussion in 36(21%) patients, bronchial breath sound in 25(17%) patients. Regarding radiological features, lobar consolidation was found in 18(12%) patients, patchy opacities in 42(28%) patients, which were radiological findings of pneumonia, while hyperinflation of lung present in 90(60%) patients, increased translucency in 82(54.6%), increased interstitial marking in 88(58.6%) patients, which were radiological findings of bronchiolitis. A total of 60(40%) admitted cases were diagnosed as pneumonia and 90(60%) cases diagnosed as bronchiolitis radiologically, which were predominant in WHO classified severe pneumonia (p<0.05). Wheeze was present in case of hyperinflation of lung in 78(83.8%), increased translucency in 67(72%) and increased interstitial marking in 70(75.2%) patients among radiological bronchiolitis (n=90). From above results we can concluded that Bronchiolitis was predominant among WHO guideline classified severe pneumonia.