Diagnosis of non-CF bronchiectasis is often delayed because of a failure to recognize the significance of symptoms. Through clinical investigation, including a HRCT scan of the chest, sweat test, studies of immune function, and ciliary function in a child with a prolonged suppurative cough, remains important. In Turkey, the most common causes of non-CF bronchiectasis are PCD and immunodeficiency, related to a high frequency of consanguinity.

Interstitial lung disease, nephrotic syndrome and junctional epidermolysis bullosa is an autosomal recessive multiorgan disorder caused by mutations in the gene for the integrin α3 subunit (ITGA3). The full spectrum of manifestations and genotype-phenotype correlations is still poorly characterized. Here, we uncovered the disease-causing role and the molecular mechanisms underlying a homozygous ITGA3 mutation leading to the single amino acid substitution, p.R463W. The patient suffered from respiratory distress and episodes of cyanosis with onset in the first week of life and had a nephrotic syndrome. Although there was no clinical evidence for cutaneous fragility, the analysis of a skin sample and of skin epithelial cells enabled the direct assessment of the authentic mutant protein. We show that the mutation altered the conformation of the extracellular β-propeller domain of the integrin α3 subunit preventing correct processing of N-linked oligosaccharides, heterodimerization with β1 integrin and maturation through cleavage into heavy and light chains in the Golgi. Confocal microscopy demonstrated that the mutant protein accumulated intracellularly, but it was not present in focal adhesions or on the cell membrane as shown by flow cytometry. These findings highlight that single amino acid changes in the integrin α3 subunit may crucially alter the structure and complex processing of this integrin, completely preventing its functionality. The present report also underscores that ITGA3 mutations may account for atypical cases solely with early onset respiratory and renal involvement.

Anaerobic and aerobic performance is impaired in PCD from the early stages. Age determines anaerobic performance. Gender is the determinant of aerobic performance. Whether skeletal muscle characteristics and sex-related changes in body composition affect anaerobic and aerobic capacity in PCD children warrants further study. What is Known: • Exercise performance is determined by anaerobic and aerobic power. • Few studies have shown that PCD patients have lower aerobic performance which is associated with impaired lung function. What is New: • The present research indicated that both anaerobic and aerobic exercise capacity determined using field testing is impaired in PCD from the early stages. • Anaerobic capacity was found to be independently associated with age in PCD. Higher aerobic performance is independently associated with male gender.

Early antibiotic treatment for Pa can eradicate the bacteria, prevent or delay the development of chronic colonization and improve the general health status. The acquisition of Pa at an older age and having symptoms at first isolation negatively affected the success of eradication. The use of intravenous antibiotics may increase the efficacy of therapy. Inhaled tobramycin for Pa eradication was approved for reimbursement in Turkey from August 2014. The relatively low eradication rate may be explained by a lack of reimbursement for inhaled tobramycin and colistin in our country during the study period.

Childhood interstitial lung diseases (chILDs) are rare and heterogeneous diseases with significant morbidity and mortality. An accurate and quick aetiological diagnosis may contribute to better management and personalised treatment. On behalf of the European Respiratory Society Clinical Research Collaboration for chILD (ERS CRC chILD-EU), this review summarises the roles of the general paediatrician, paediatric pulmonologists and expert centres in the complex diagnostic workup. Each patient's aetiological chILD diagnosis must be reached without prolonged delays in a stepwise approach from medical history, signs, symptoms, clinical tests and imaging, to advanced genetic analysis and specialised procedures including bronchoalveolar lavage and biopsy, if necessary. Finally, as medical progress is fast, the need to revisit a diagnosis of “undefined chILD” is stressed.