TAPSE/SPAP ratio stratifies mortality risk in mild-to-moderate idiopathic pulmonary fibrosis.

BACKGROUND: Due to paucity of literature data, we aimed at evaluating the prognostic role of the ratio of tricuspid annular plane systolic excursion (TAPSE) to systolic pulmonary artery pressure (SPAP) in idiopathic pulmonary fibrosis (IPF) patients without severe pulmonary hypertension and at assessing its correlation with effective arterial elastance index (EaI). METHODS: Multi-instrumental data obtained in 60 IPF patients (73.2 ± 6.8 years) and 60 matched controls were retrospectively analysed. Primary endpoint was all-cause mortality, while secondary endpoint was the composite of all-cause mortality and re-hospitalisations for all-causes over medium-term follow-up. RESULTS: ;At baseline, TAPSE/SPAP was significantly lower in patients with IPF than in controls (0.36 ± 0.25 vs. 0.77 ± 0.18 mm/mmHg; P < 0.001). TAPSE/SPAP was inversely correlated with EaI (r = -0.96) in IPF patients. During follow-up (3.5 ± 1.5 years), 21 patients died and 25 were re-hospitalised due to cardiopulmonary causes. TAPSE/SPAP was independently associated with both primary (HR 0.79, 95%CI 0.65-0.97) and secondary (HR 0.94, 95%CI 0.92-0.97) endpoints. A TAPSE/SPAP ratio of <0.20 and <0.44 mm/mmHg showed the greatest sensitivity and specificity for predicting primary (AUC 0.98) and secondary (AUC 0.99) endpoints, respectively. CONCLUSIONS: TAPSE/SPAP is a strong predictor of adverse outcomes in mild-to-moderate IPF. The strong correlation between TAPSE/SPAP and EaI might be an expression of a systemic fibrotic process which involves the heart, lungs and circulation.

High-resolution CT in smoking-related interstitial lung diseases.

In addition to chronic obstructive pulmonary disease (COPD) and bronchogenic carcinoma, smoking can also cause interstitial lung diseases (ILDs) such as respiratory bronchiolitis (RB), RB with ILD (RB-ILD), desquamative interstitial pneumonia (DIP), Langerhans cell granulomatosis (LCG) and idiopathic pulmonary fibrosis-usual interstitial pneumonia (IPF-UIP). However, smoking seems to have a protective effect against hypersensitivity pneumonitis (HP), sarcoidosis and organising pneumonia (OP). High-resolution computed tomography (HRCT) has a pivotal role in the differential diagnosis. RB is extremely frequent in smokers, and is considered a marker for smoking exposure. It has no clinical relevance in itself since most patients with RB are asymptomatic. It is frequent to observe the association of RB with other smoking-related diseases, such as LCG or pulmonary neoplasms. In RB-ILD, HRCT features are more conspicuous and diffuse than in RB, but there is no definite cut-off between the two entities and any distinction can only be made by integrating imaging and clinical data. RB, RB-ILD and DIP may represent different degrees of the same pathological process, consisting in a bronchiolar and alveolar inflammatory reaction to smoking. Smoking is also a well-known risk factor for pulmonary fibrosis. Multidisciplinary discussion and follow-up can generally solve even the most difficult cases.

Radiological diagnosis of fibrosing interstitial lung diseases: innovations and controversies.

Following the introduction of new effective antifibrotic drugs, interest in fibrosing interstitial lung diseases (FILD) has been renewed. In this context, radiological evaluation of FILD plays a cardinal role. Radiological diagnosis is possible in about 50% of the cases, which allows the initiation of effective therapy, thereby avoiding invasive procedures such as surgical lung biopsy. Usual interstitial pneumonia (UIP) pattern may be diagnosed based on clinical, radiological, and pathological data. High-resolution computed tomography features of UIP have been widely described in literature; however, interpreting them remains challenging, even with specific expertise on the subject. Diagnostic difficulties are understandable given the continuous evolution of FILD classifications and their complexity. Both early-stage diseases and advanced or combined patterns are not easily classifiable, and many end up being labelled 'indeterminate´ or 'unclassifiable´. Especially in these cases, optimal patient management involves collaboration and communication between different specialists. Here, we discuss the most critical aspects of radiological interpretation in FILD diagnosis based on the most recent classifications. We believe that the clinicians´ awareness of radiological diagnostic issues of FILD would improve comprehension and dialogue between physicians and radiologists, leading to better clinical practice.

Severe idiopathic pulmonary fibrosis: A clinical approach.

Idiopathic pulmonary fibrosis (IPF) is a devastating progressive disease associated with a high mortality rate. Novel antifibrotic therapies have been recently demonstrated to slow disease progression and improve survival. However, the management of IPF remains a difficult challenge, since lung complications can still occur, particularly in patients with advanced-stage disease. This paper highlights the most common complications and difficult tasks related to severe IPF such as acute exacerbation of the disease, development of lung cancer, rapid disease progression, and indication for lung transplantation.

Efficacy of pirfenidone for idiopathic pulmonary fibrosis: An Italian real life study.

BACKGROUND: In this retrospective Italian study, which involved all major national interstitial lung diseases centers, we evaluated the effect of pirfenidone on disease progression in patients with IPF. METHODS: We retrospectively studied 128 patients diagnosed with mild, moderate or severe IPF, and the decline in lung function monitored during the one-year treatment with pirfenidone was compared with the decline measured during the one-year pre-treatment period. RESULTS: At baseline (first pirfenidone prescription), the mean percentage forced vital capacity (FVC) was 75% (35-143%) of predicted, and the mean percentage diffuse lung capacity (DLCO) was 47% (17-120%) of predicted. Forty-eight patients (37.5%) had mild disease (GAP index stage I), 64 patients (50%) had moderate IPF (stage II), and 8 patients (6.3%) had severe disease (stage III). In the whole population, pirfenidone attenuated the decline in FVC (p = 0.065), but did not influence the decline in DLCO (p = 0.355) in comparison to the pre-treatment period. Stratification of patients into mild and severe disease groups based on %FVC level at baseline (>75% and ≤75%) revealed that attenuation of decline in FVC (p = 0.002) was more pronounced in second group of patients. Stratification of patients according to GAP index at baseline (stage I vs. II/III) also revealed that attenuation of decline in lung function was more pronounced in patients with more severe disease. CONCLUSIONS: In this national experience, pirfenidone reduced the rate of annual FVC decline (p = 0.065). Since pirfenidone provided significant treatment benefit for patients with moderate-severe disease, our results suggest that the drug may also be effective in patients with more advanced disease.

IPF: new insight on pathogenesis and treatment.

Recent years have seen a robust influx of exciting new observations regarding the mechanisms that regulate the initiation and progression of pulmonary fibrosis but the pathogenesis remains poorly understood. The search for an alternative hypothesis to unremitting, chronic inflammation as the primary explanation for the pathophysiology of idiopathic pulmonary fibrosis (IPF) derives, in part, from the lack of therapeutic efficacy of high-dose immunosuppressive therapy in patients with IPF. The inflammatory hypothesis of IPF has since been challenged by the epithelial injury hypothesis, in which fibrosis is believed to result from epithelial injury, activation, and/or apoptosis with abnormal wound healing. This hypothesis suggests that recurrent unknown injury to distal pulmonary parenchyma causes repeated epithelial injury and apoptosis. The resultant loss of alveolar epithelium exposes the underlying basement membrane to oxidative damage and degradation. Emerging concepts suggest that IPF is the result of epithelial-mesenchymal interaction. The initiation of this fibrotic response may depend upon genetic factors and environmental triggers; the role of Th1 or Th2 cell-derived cytokines may also be important. This process appears to be unique to usual interstitial pneumonia/IPF. It is clear that IPF is a heterogeneous disease with variations in pathology, high-resolution computed tomography findings, and patterns of progression. Idiopathic pulmonary fibrosis is a complex disorder, and no unifying hypothesis has been identified at present that explains all the abnormalities.

Smoking-related interstitial lung diseases.

In pulmonary pathology, a wide spectrum of morphological changes is related to the consequences of smoking, and recognizing them on surgical specimens and on small transbronchial biopsies represents a challenge for the pathologist. Respiratory bronchiolitis, also referred to as smoker's bronchiolitis, is a common histologic feature found in the lung tissue of cigarette smokers. When identified as the sole histopathologic finding in the clinical setting of symptomatic interstitial lung disease, a diagnosis of respiratory bronchiolitis-interstitial lung disease is made. Since smoking is recognized to cause a variety of histologic patterns encompassing respiratory bronchiolitis, respiratory bronchiolitis-interstitial lung disease, desquamative interstitial pneumonia and pulmonary Langerhans cell hystiocytosis, smoking-related interstitial lung disease may be a useful concept to keep in mind for the pathologists. The relationship of smoking with each of these entities has been largely established on the basis of epidemiologic evidence. Although they have been retained as distinct and separate conditions in various classifications of interstitial lung diseases, these entities share a number of clinical, radiologic, and pathologic features suggesting that they represent a spectrum of patterns of interstitial lung disease occurring in predisposed individuals who smoke. Evaluation of histologic features, particularly in surgical lung biopsy samples, is important in making the distinction between these disorders. However, even after tissue biopsy, it may sometimes be difficult to clearly separate these entities. Recently, respiratory bronchiolitis-interstitial lung disease with fibrosis has been described and postulated that this is a smoking-related condition distinct from fibrotic non-specific interstitial pneumonia.

Bronchoalveolar lavage in intensive care units.

Pneumonia is common in those patients placed in intensive care units, especially in mechanically ventilated patients. The high mortality rate of ventilator-associated pneumonia requires a rapid initiation of the appropriate antibiotic treatment. Patients who do not respond to initial antibiotic regimens could have the additional benefit of the use of invasive techniques such as bronchoalveolar lavage. Moreover, BAL is of clinical use to identify several non-infectious pulmonary conditions that may mimic pneumonia in these patients. Such conditions include pulmonary haemorrhages, acute eosinophilic pneumonia, malignancy, drug-induced toxicity, adult respiratory distress syndrome and cardiogenic pulmonary oedema. It is important to distinguish these conditions from pneumonia because the management and prognosis of these entities is quite different.

Predominant TH1 cytokine pattern in peripheral blood from subjects with chronic obstructive pulmonary disease.

BACKGROUND: Previous studies have provided evidence for an inflammatory process in the large airways of subjects with chronic obstructive pulmonary disease (COPD), consisting predominantly of activated T cells. No data are available on the TH1 /TH2 T-cell cytokine pattern in this disease. OBJECTIVE: We sought to characterize the TH1 /TH2 T-cell cytokine pattern in subjects with COPD. METHODS: We examined the IFN-gamma and IL-4 expression in peripheral blood CD4+ and CD8+ T cells from 20 patients with COPD and 25 control subjects by using a flow cytometric method of intracellular cytokine detection. We also examined the expression of 2 surface activation markers (CD25 and HLA-DR) on peripheral blood CD4+ and CD8+ T cells. RESULTS: There was an increased percentage of IFN-gamma-producing cells (30.3% [range, 12.9% to 60.4%] vs 19.1% [range, 4% to 31.2%], P =.003) and a decreased percentage of IL-4-producing cells (4.55% [range, 0.6% to 11.3%] vs 9.5% [2.1% to 21.3%], P =.0008) among peripheral blood CD4+ T cells from the patients with COPD compared with control subjects. There was no significant difference between the 2 groups in the percentage of peripheral blood CD8+ T cells producing IFN-gamma or IL-4 or in the percentage of peripheral blood CD4+ and CD8+ T cells expressing CD25 and HLA-DR. CONCLUSION: These findings provide evidence for a TH1 -like immune response of peripheral blood CD4+ T cells in subjects with COPD.