Wheeze is a common symptom in infants, but not all wheezers develop asthma. Indeed, up to 50% of wheezing children outgrow their symptoms by school age. How to predict if early wheeze will become asthma is still a matter of vivid debate. In this work, we sought to assess the clinical and pathological factors that might predict the future development of asthma in children. Eighty children (mean age 3.8 ± 1 yr) who underwent a clinically indicated bronchoscopy were followed prospectively for a median of 5 years. At baseline, clinical characteristics with a particular focus on wheezing and its presentation (episodic or multitrigger) were collected, and structural and inflammatory changes were quantified in bronchial biopsies. Follow-up data were available for 74 of the 80 children. Children who presented with multitrigger wheeze were more likely to have asthma at follow-up than those with episodic wheeze (P = 0.04) or without wheeze (P < 0.0001). Children with asthma also had lower birth weights (P = 0.02), a lower prevalence of breastfeeding (P = 0.02), and a trend for increased IgE (P = 0.07) at baseline than those with no asthma. Basement membrane thickness and airway eosinophils at baseline were increased in children who developed asthma at follow-up (P = 0.001 and P = 0.026, respectively). Multivariate analysis showed that among all clinical and pathological factors, multitrigger wheezing, basement membrane thickening, and reduced birth weight were predictive of future asthma development. We conclude that multitrigger wheeze and reduced birth weight are clinical predictors of asthma development. Basement membrane thickening in early childhood is closely associated with asthma development, highlighting the importance of airway remodeling in early life as a risk factor for future asthma.

Pneumothorax (PNX) and pneumomediastinum (PNM) are potential complications of COVID-19, but their influence on patients’ outcomes remains unclear. The aim of the study was to assess incidence, risk factors, and outcomes of severe COVID-19 complicated with PNX/PNM. Methods: A retrospective multicenter case-control analysis was conducted in COVID-19 patients admitted for respiratory failure in intermediate care units of the Treviso area, Italy, from March 2020 to April 2021. Clinical characteristics and outcomes of patients with and without PNX/PNM were compared. Results: Among 1213 patients, PNX and/or PNM incidence was 4.5%. Among these, 42% had PNX and PNM, 33.5% only PNX, and 24.5% only PNM. COVID-19 patients with PNX/PNM showed higher in-hospital (p = 0.02) and 90-days mortality (p = 0.048), and longer hospitalization length (p = 0.002) than COVID-19 patients without PNX/PNM. At PNX/PNM occurrence, one-third of subjects was not mechanically ventilated, and the respiratory support was similar to the control group. PNX/PNM occurrence was associated with longer symptom length before hospital admission (p = 0.005) and lower levels of blood lymphocytes (p = 0.017). Conclusion: PNX/PNM are complications of COVID-19 associated with a worse prognosis in terms of mortality and length of hospitalization. Although they are more frequent in ventilated patients, they can occur in non-ventilated, suggesting that mechanisms other than barotrauma might contribute to their presentation.

Rationale: Outdoor air pollution contributes to asthma development and exacerbations, yet its effects on airway pathology have not been defined in children. Objectives: To explore the possible link between air pollution and airway pathology, we retrospectively examined the relationship between environmental pollutants and pathological changes in bronchial biopsy specimens from children undergoing a clinically indicated bronchoscopy. Methods: Structural and inflammatory changes (basement membrane [BM] thickness, epithelial loss, eosinophils, neutrophils, macrophages, mast cells, and lymphocytes) were quantified in biopsy specimens by using immunohistochemistry. The association between exposure to particulate matter less than 10 μm in aerodynamic diameter (PM10), SO2 and NO2 and biopsy findings was evaluated by using a generalized additive model with Gamma family to allow for overdispersion, adjusted for atmospheric pressure, temperature, humidity, and wheezing. Results: Overall, 98 children were included (age 5.3 ± 2.9 yr; 53 with wheezing/45 without wheezing). BM thickness increased with prolonged exposure to PM10 (rate ratio [RR], 1.29; 95% confidence interval [CI], 1.09–1.52), particularly in children with wheezing. Prolonged exposure to PM10 was also associated with eosinophilic inflammation in children with wheezing (RR, 3.16; 95% CI, 1.35–7.39). Conversely, in children without wheezing, increased PM10 exposure was associated with a reduction of eosinophilic inflammation (RR, 0.12; 95% CI, 0.02–0.6) and neutrophilic inflammation (RR, 0.36; 95% CI, 0.14–0.89). Moreover, NO2 exposure was also linked to reductions in neutrophil infiltration (RR, 0.57; 95% CI, 0.34–0.93) and eosinophil infiltration (RR, 0.33; 95% CI, 0.14–0.77). Conclusions: Different patterns of association were observed in children with wheezing and in children without wheezing. In children without wheezing, exposure to PM10 and NO2 was linked to reduced eosinophilic and neutrophilic inflammation. Conversely, in children with wheezing, prolonged exposure to PM10 was associated with increased BM thickness and eosinophilic inflammation, suggesting that it might contribute to asthma development by promoting airway remodeling and inflammation.

SARS-CoV-2 may lead to a large spectrum of respiratory manifestations, including pulmonary sequelae. We conducted a single-center longitudinal study of survivors from severe COVID-19 cases who underwent a chest CT during hospitalization (CT_H). Three months after being discharged, these patients were evaluated by a clinical examination, pulmonary function tests and a chest-CT scan (CT_FU). Sixty-two patients were enrolled. At follow-up, 27% complained of exertional dyspnoea and 12% of cough. Dyspnoeic patients had a lower forced expiratory flow (FEF)_25–75 (p = 0.015), while a CT scan (p = 0.016 showed that patients with cough had a higher extent of bronchiectasis. Lung volumes and diffusion of carbon monoxide (DLCO) at follow-up were lower in patients who had been invasively ventilated, which correlated inversely with the length of hospitalization and ground-glass extension at CT_H. At follow-up, 14.5% of patients had a complete radiological resolution, while 85.5% presented persistence of ground-glass opacities, and 46.7% showed fibrotic-like alterations. Residual ground-glass at CT_FU was related to the length of hospitalization (r = 0.48; p = 0.0002) and to the need for mechanical ventilation or high flow oxygen (p = 0.01) during the acute phase. In conclusion, although patients at three months from discharge showed functional impairment and radiological abnormalities, which correlated with a prolonged hospital stay and need for mechanical ventilation, the persistence of respiratory symptoms was related not to parenchymal but rather to airway sequelae.

Asthma is a heterogeneous condition characterized by reversible airflow limitation, with different phenotypes and clinical expressions. Although it is known that asthma is influenced by age, gender, genetic background, and environmental exposure, the natural history of the disease is still incompletely understood. Our current knowledge of the factors determining the evolution from wheezing in early childhood to persistent asthma later in life originates mainly from epidemiological studies. The underlying pathophysiological mechanisms are still poorly understood. The aim of this review is to converge epidemiological and pathological evidence early in the natural history of asthma to gain insight into the mechanisms of disease and their clinical expression.