Airway hyperresponsiveness, remodeling and inflammation in infants with wheeze

• Published in: Clinical and experimental allergy 2020-05, Vol.50 (5), p.558-566
• Main Authors: Malmström, Kristiina, Lohi, Jouko, Malmberg, Leo Pekka, Kotaniemi‐Syrjänen, Anne, Lindahl, Harry, Sarna, Seppo, Pelkonen, Anna S., Mäkelä, Mika J.
• Format: Article
• Language: English
• Subjects: Age; Asthma; Atopy; Children; Compression; Corticosteroids; Cystic fibrosis; Dyskinesia; eosinophils; Infants; Inflammation; Leukocytes (eosinophilic); Mast cells; Methacholine; paediatrics; remodeling; Respiration; Respiratory function; Respiratory tract; Smooth muscle
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/cea.13598

Background The relationship of airway hyperresponsiveness to airway remodeling and inflammation in infants with wheeze is unclear. Objective To investigate airway hyperresponsiveness, remodeling and inflammation in infants with wheeze and troublesome breathing. Methods Inclusion criteria were as follows: full‐term, 3‐23 months of age; doctor ‐diagnosed wheeze and persistent recurrent troublesome breathing; without obvious structural defect, suspicion of ciliary dyskinesia, cystic fibrosis, immune deficiency or specified use of corticosteroids. Airway hyperresponsiveness (AHR) was evaluated by performing a methacholine bronchial challenge test combined with whole body plethysmography and rapid thoracoabdominal compression. Endobronchial biopsies were analysed for remodeling (thickness of reticular basement membrane and amount of airway smooth muscle) and for inflammation (numbers of inflammatory cells). Correlation analyses were performed. Results Forty‐nine infants fulfilled the inclusion criteria for the present study. Median age was 1.06 years (IQR 0.6; 1.5). Lung function was impaired in 39/49 (80%) children, at the median age of 1.1 years. Methacholine challenge was successfully performed in 38/49 children. Impaired baseline lung function was correlated with AHR (P = .047, Spearman). In children with the most sensitive quartile of AHR, the percentage of median bronchial airway smooth muscle % and the number of bronchial mast cells in airway smooth muscle were not significantly higher compared to others (P = .057 and 0.056, respectively). No association was found between AHR and thickness of reticular basement membrane or inflammatory cells. Only a small group of children with both atopy and AHR (the most reactive quartile) had thicker airway smooth muscle area than non‐atopics with AHR (P = .031). Conclusions and Clinical Relevance These findings do not support the concept that AHR in very young children with wheeze is determined by eosinophilic inflammation or clear‐cut remodeling although it is associated with impaired baseline lung function. The possible association of increased airway smooth muscle area among atopic children with AHR remains to be confirmed.