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Nonspecific interstitial pneumonia (NSIP) was initially defined in 1994 as a histopathologic pattern, characterized by the presence of varying proportions of lung interstitial inflammation and fibrosis, with a temporally uniform lung involvement, that can be found in the presence of a wide variety of clinical and radiologic contexts. Idiopathic NSIP, considered as a "provisional clinical diagnosis" until recently, has now been recognized as a distinct clinical entity, interestingly occurring mostly in middle-aged and never-smoker women, with dyspnoea, cough, ground glass at high resolution CT scan of the chest, and with a very good prognosis. Though this recent evidence, the diagnosis of idiopathic NSIP is still based on histology obtained from surgical lung biopsy, as recommended by the American Thoracic Society/European Respiratory Society statement: are less invasive procedures, such as transbronchial lung biopsies and bronchoalveolar lavage, useful tools in the initial approach of this clinical entity?

Mutations in the gene encoding surfactant protein C (SP-C) SFTPC have been found to be associated with chronic interstitial lung disease. A 5-year-old girl oxygen dependent from birth and affected by interstitial lung disease (ILD) is heterozygous for a T to C change in exon 3 resulting in the substitution of threonine for isoleucine at codon 73 (173T), already described in association with ILD. We studied 25 members of her family where the 173T mutation in the SP-C gene is associated to chronic pulmonary diseases. Five members in the mother's family showed respiratory diseases with great diversity in clinical features: her mother was affected by restrictive pneumopathy and emphysema, her grand-mother by asthma and recurrent pneumonia, 2 uncles underwent lung transplantation in the adult age, an aunt was clinically diagnosed having pulmonary fibrosis. All the family members affected by pulmonary diseases and one with no clinical symptoms showed the presence of the mutation 173T. Among the other family members the mutation was found in six subjects for whom no clinical data were available, yet. Our results confirm that heterozygosity for the mutation 173T may cause chronic inflammation of the lung or progressive pulmonary fibrosis. In addition, the possibility to study a large pedigree allowed us to perform a genotype-phenotype correlation indicating a marked phenotypic variability. The diversity in symptoms, age at onset, clinical course, duration of lung disease in the relatives sharing this mutation indicates an incomplete penetrance of the mutation. This might be due to the influence of other genetic factors thus indicating that the phenotype may be complicated by additional components.