Clinical profile of unclassifiable interstitial lung disease: Comparison with chronic fibrosing idiopathic interstitial pneumonias.

Objective Unclassifiable interstitial lung disease (ILD) is a common problem in clinical practice. These patients pose a distinct challenge with regard to appropriate evaluation and management. We investigated the clinical features and prognosis of unclassifiable ILD and compared its clinical profile with that of idiopathic pulmonary fibrosis (IPF) and idiopathic nonspecific interstitial pneumonia (NSIP). Methods Patients with IPF (n = 40), NSIP (n = 14), and unclassifiable ILD (n = 27) were selected from an ongoing database. Baseline clinical features, pulmonary function, and the extent of fibrosis on high-resolution computed tomography (HRCT) were evaluated. Mortality was estimated based on the ILD-Gender, Age, Physiology (ILD-GAP) index and composite physiologic index (CPI). Results IPF was associated with the worst survival (hazard ratio [HR] = 4.361 compared with NSIP), followed by unclassifiable cases (HR = 1.251 compared with NSIP). Increasing mortality was significantly impacted by age (HR = 1.04 per 1-year increase), lower carbon monoxide diffusing capacity of the lung (HR = 0.97), HRCT interstitial score (HR = 1.119 per 1-point increase), ILD-GAP score (HR = 1.570 per 1-point increase), and CPI (HR = 1.039 per 1-point increase). Conclusions Patients with unclassifiable ILD had an intermediate prognosis between that of IPF and NSIP. Patients at high risk of mortality can be identified using baseline clinical, physiological, and radiological features.

Interstitial lung disease as first clinical manifestation within the antisynthetase syndrome--dermatomyositis.

Diffuse interstitial pneumopathies within the diseases of the connective tissue are often a diagnosis challenge, sometimes being the initial or dominant manifestation of the underlying autoimmune disease. The case of a young man shall be presented with relatively quick dyspnoea which has appeared under the conditions of an efficient physical status and without any notable pathological history. The cause of the dyspnoea is found to be a interstitial lung disease with radiological and histopathological pattern of non-specific interstitial pneumonia. The disease screening system discovers Ac anti Ro-52 which commits research in the direction of an autoimmune disease, confirmed by highlighting Ac anti PL-7 as being an antisynthetase syndrome. Subgroup of idiopathic inflammatory myopathies, the antisynthetase syndrome is a rare chronic autoimmune disease, which is characterised by the presence of antibodies directed against aminoacyl-t-RNA-synthetases (family of intracytoplasmic enzymes with a vital role in the protein synthesis). Shortly after specifying the relevant immunological status, the consistent clinical expression with dermatomyositis is also configured. The treatment is commenced with systemic corticoid and azathioprine; despite the treatment we are witnessing a slowly progressive clinical and functional deterioration.

Short telomeres in pulmonary fibrosis: from genetics to clinical significance.

Pulmonary fibrosis has been linked molecularly and pathophysiologically by abnormal telomere maintenance. Short telomere lengths are commonly found in both the familial and sporadic forms, telomerase mutations being the most common identifiable genetic cause of the disease. Telomeres are repeated nucleotide sequences that cap the ends of chromosomes and protect them from damage. Telomeres are eroded with cell division and shorten with age. Telomere integrity is mediated by the telomerase complex, a specialized polymerase that adds sequences to the ends of chromosomes. Mutations in the genes encoding telomerase (TERT and TERC) cause pulmonary fibrosis through low telomerase activity, accelerated telomere shortening and exhaustion of lung stem cells. Mutations in TERTor TERC account for only 19% of familial pulmonary fibrosis cases, and it is likely that additional environmental, genetic and epigenetic factors contribute to telomere erosion and to disease phenotype. Identification of short telomeres has potential clinical implications in pulmonary fibrosis: it may be a marker for an increased predisposition toward the development of the disease, it might affect risk stratification as it has been associated with lower survival rates and post-transplant complications that reflect the syndromic nature of this molecular defect.

Clinical relevance of maximal inspiratory pressure: determination in COPD exacerbation.

Muscle dysfunction represents a pathophysiological feature of chronic obstructive pulmonary disease (COPD). Muscle impairment contributes to decreased effort capacity in these patients at least in the same proportion as pulmonary function limitation. Maximal inspiratory pressure (MIP) is a reliable, noninvasive parameter for assessing the respiratory muscle capacity. The aim of the present study was to determine the role of MIP in effort capacity decrease in COPD patients. MIP was measured in 121 COPD patients without hyperinflation (RV < 150%) together with the following investigations: body plethysmography, body impedance analysis, dynamometry, 6-minute walking test (6MWT), determination of SaO(2) and serum levels of highly sensitive C-reactive protein (hsCRP). MIP (kPa) was significantly decreased in moderate-severe stages (6.19 +/- 2.42, COPD II; 5.35 +/- 2.49, COPD III; 4.56 +/- 1.98, COPD IV vs 7.90 +/- 2.61 in controls, P < 0.001), whereas the muscle force assessed by dynamometry was decreased only in advanced stages of disease (0.47 +/- 0.12, COPD III; 0.41 +/- 0.07, COPD IV vs 0.71 +/- 0.16 in controls, P < 0.001). The values of MIP correlated (r = 0.53, P = 0.0003) with the distance walked in 6MWT. MIP may provide additive information concerning the general profile of muscle dysfunction in COPD patients.