Respiratory Morbidity and Exhaled Nitric Oxide in the First 2 Years of Life: the Generation R Study

textabstractAsthma is a lung disease characterized by chronic inflammation of the airways associated with bronchial hyperresponsiveness. The airflow obstruction within the lungs is responsible of recurrent episodes of wheezing, breathlessness, chest tightness and coughing. The physiopathological changes of the airways in asthma are mediated by many cells and cellular elements. It has been argued that asthma is a syndrome comprising a number of separate conditions, rather than a single disease with a broad range of severity. It has long been thought that the inappropriate response of the specific immune system to harmless antigens leading to the polarization of T‐cells toward a T‐helper 2 (Th2) phenotype was the central mechanism of asthma. However, in the last years the hypothesis of asthma as one unifying disease concept has disappeare. Novel disease and bronchial inflammation pathways, many of which are independent of adaptive immunity, have been reported. The concept of disease endotypes has been recently introduced and subtypes of asthma with different and specific pathophysiology, immunology, clinical features and response to treatment have been described. A simple categorization of the different inflammatory patterns in asthmatics based on sputum eosinophil and neutrophil proportions has been provided and four inflammatory subtypes have been identified: neutrophilic, eosinophilic, mixed granulocytic and paucigranulocytic asthma. A recent review by Haldar and Pavord suggested that non‐eosinophilic asthma represents a stable phenotype associated with distinct etiologic factors and less airway pathology. Also, it has been suggested that severe asthma should no longer be considered as the result of a progressive process, but rather as a separate pathological entity with distinct physiologic and clinical characteristics. These heterogeneous inflammatory patterns have been also reported by Brasier et al, who evaluated bronchoalveolar lavage (BAL) samples in mild to severe asthmatic patients. They showed that cytokine expression patterns in BAL could be used to identify distinct types of asthma and identify distinct subsets of methacholine hyperresponders. Despite improved understanding of pathophysiology, immunology and genetics of asthma in childhood, we still do not know the basic mechanisms underlying the development of the disease