IC4: a new combined predictive index of mortality in idiopathic pulmonary fibrosis.

BACKGROUND: While a number of individual patient characteristics are associated with survival in idiopathic pulmonary fibrosis (IPF), their incorporation into combined indexes, such as the GAP index, has been shown to increase the predictive capacity. It is unknown whether the predictive capacity of GAP-derived indexes that also include anthropometric and exercise parameters is superior to the original instrument. METHODS: We tested the four-year survival predictive capacity of a modified, adimensional and multiplicative GAP index (IC4) that included percent forced vital capacity (FVC%), diffusing capacity of the lung for carbon monoxide (DLCO%), Body Mass Index (BMI), and six-minute walk distance (6MWD) in 90 IPF patients recruited from two centers in France and Italy. RESULTS: In ROC comparisons, the AUC of the IC4 (0.859, 95% CI 0.770-0.924 P<0.0001) was significantly higher than the AUCs of the individual components, their two-three component combinations, and the original GAP index, with 77% sensitivity and 89% specificity. Mean survival was 14.0±11.7, 23.2±12.7, 34.9±14.8, and 40.8±12.9 months, and survival rate was 0%, 14%, 39% and 73%, in IC4 quartile 1, 2, 3, and 4, respectively. CONCLUSIONS: The IC4, a combined non-dimensional index incorporating FVC%, DLCO%, BMI and 6MWD, provides superior capacity to predict mortality, when compared to its individual components, their other combinations, and the GAP index, in patients with IPF.

The Aggregate Index of Systemic Inflammation (AISI): A Novel Prognostic Biomarker in Idiopathic Pulmonary Fibrosis.

Variable patterns of disease progression are typically observed in patients with idiopathic pulmonary fibrosis (IPF). We sought to determine the prognostic capacity of blood cell count indexes, derived from routine complete blood cell (CBC) count, in a cohort of IPF patients. The neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) were calculated at baseline in a consecutive series of 82 IPF patients followed for four years. After adjusting for age, gender, body mass index, smoking status, and disease stage, only the AISI was significantly associated with mortality (HR 1.0013, 95% CI 1.0003-1.0023, p = 0.015). Patients with AISI <434 and ≥434 had a median survival from the diagnosis of 35.3 ± 15.2 and 26.6 ± 16.3 months (p = 0.015), and a four-year survival rate of 54% and 34%, respectively. The AISI, easily derivable from routine laboratory tests, is independently associated with mortality in patients with IPF. Prospective studies in larger cohorts are required to confirm this association.

The levels of trace elements in sputum as biomarkers for idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a rare lung disease that quickly leads to death. This paper addressed the issue of whether the levels of trace elements in sputum samples are suitable biomarkers for IPF disease. The sputum Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn concentrations were measured by sector field inductively coupled plasma mass spectrometry in populations sampled in Sardinia Island (Italy) including 31 patients with IPF, 31 patients with other lung-related diseases and 30 age- and gender-matched healthy controls. Risk factors in the disease as gender, age, severity and duration of the disease were assessed. Results showed that IPF patients had significantly increased sputum levels of Cd, Cr, Cu and Pb respect to controls. In males, but not in females, sputum levels of Cd, Cr and Cu were significantly higher in IPF cases respect to controls. In addition, Cr and Pb were increased in male patients with IPF compared to male patients with other lung diseases. Regarding Zn, it was found higher with the more serious stage of disease. Moreover, the ratios Cu/Zn, Fe/Mn and Cu/Mn were significantly increased in IPF patients and in non-IPF patients than in control subjects. These data showed clear increases in the concentration of some trace elements in sputum from patients with IPF and patients with other lung-related diseases that may contribute to the injury. The non-invasiveness of the sputum analysis is beneficial for its use as biomarker of trace element status in diseased patients for both the researcher and the clinic.

Blood Cell Count Derived Inflammation Indexes in Patients with Idiopathic Pulmonary Fibrosis.

PURPOSE: Inflammation and immunity play a pivotal but yet unclear role in idiopathic pulmonary fibrosis (IPF), a chronic disorder characterized by progressive damage of lung parenchyma and severe loss of lung function despite optimal treatment. However, the pathophysiological and predictive role of combined blood cell count indexes of inflammation in IPF is uncertain. METHODS: Seventy-three patients with IPF and 62 healthy subjects matched for age, gender and smoking status were included in this cross-sectional study. RESULTS: We found significant differences in neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), monocyte to lymphocyte ratio (MLR), platelet to lymphocyte ratio (PLR), systemic inflammation response index (SIRI) and aggregate index of systemic inflammation (AISI) between IPF patients and healthy controls. In logistic regression, all combined blood inflammation indexes, barring PLR, were independently associated with the presence of IPF after adjusting for age, gender, body mass index and smoking status. Furthermore, significant associations between FVC% and NLR, LMR, SIRI and AISI, and between DLCO% and NLR, dNLR, LMR, SIRI and AISI, were observed. CONCLUSIONS: In conclusion, our data indicate significant alterations of combined blood cell count indexes of inflammation in IPF.

Treatment of COPD and COPD-heart failure comorbidity in primary care in different stages of the disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease that may have a negative impact on both patients' quality of life and survival. Patients with COPD frequently suffer from heart failure (HF), likely owing to several shared risk factors. AIM: To evaluate the differences in treatment of COPD with and without HF comorbidity according to COPD severity in the general practitioner setting. METHODS: We conducted an observational, retrospective study using data obtained from the Italian Health Search Database, which collects information generated by the routine activity of general practitioners. The study sample included 225 patients with COPD, alone or combined with HF. FINDINGS: It has been found that the prevalence of some comorbidities such as diabetes and HF significantly increases with the severity of COPD. Regarding pharmacological treatment, a reduction in the prescription of individually administered long-acting ß 2-agonists (LABAs) and long-acting anticholinergics (LAMAs) has been observed with increasing severity of the disease. Moreover, an increase in the prescription of both the combination of the two bronchodilators (LABA + LAMA) and their association with inhaled corticosteroids has been observed with increasing severity of COPD. The prescription of ß-blockers in patients with COPD suffering from HF comorbidity decreases from 100% in stage I to less than 50% in the other stages of COPD. This study shows that general practitioners do not follow the guidelines recommendations for the management of patients with COPD in the different stages of the disease, with and without HF comorbidity, as well as in the management of HF. Further efforts must be made to ensure adequate treatment for these patients.

Oxidative stress-linked biomarkers in idiopathic pulmonary fibrosis: a systematic review and meta-analysis.

AIM: The aim of this meta-analysis was to investigate associations between idiopathic pulmonary fibrosis (IPF) and markers of oxidative stress (OS) measured in different biological samples. METHODS: A systematic search of publications listed in PubMed, Web of Science, Scopus and Google Scholar from inception to December 2017 was conducted. RESULTS: Significant differences between IPF patients and controls were observed for all biomarkers (thiobarbituric acid reactive substances, hydroperoxides and glutathione), barring systemic isoprostanes. CONCLUSION: This meta-analysis showed a consistent increase in the concentrations of OS markers or a reduction in antioxidant markers, in patients with IPF, independent of the type of biological sample. Pending the results of further studies, OS biomarkers might be useful for the diagnosis and monitoring of IPF.

A case-report of a pulmonary tuberculosis with lymphadenopathy mimicking a lymphoma.

Clinical and radiological manifestations of tuberculosis (TB) are heterogeneous, and differential diagnosis can include both benign and malignant diseases (e.g., sarcoidosis, metastatic diseases, and lymphoma). Diagnostic dilemmas can delay appropriate therapy, favoring Mycobacterium tuberculosis transmission. We report on a case of TB in an immunocompetent, Somalian 22-year-old boy admitted in the respiratory unit of an Italian university hospital. His symptoms and clinical signs were thoracic pain, weight loss, latero-cervical, mediastinal, and abdominal lymphadenopathy. Smear microscopy and PCR were negative for Mycobacterium tuberculosis. The unclear histological pattern, the unusual clinical presentation, the CT scan signs, the BAL lymphocytes suggested the suspicion a lymphoma. Culture conversion proved Mycobacterium tuberculosis infection. This case report highlights the risk of misdiagnosis in patients with generalized lympho-adenopathy and pulmonary infiltrates, particularly in Africans young patients.