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.

Clinical course of IPF in Italian patients during 12 months of observation: results from the FIBRONET observational study.

BACKGROUND: FIBRONET was an observational, multicentre, prospective cohort study investigating the baseline characteristics, clinical course of disease and use of antifibrotic treatment in Italian patients with idiopathic pulmonary fibrosis (IPF). METHODS: Patients aged ≥ 40 years diagnosed with IPF within the previous 3 months at 20 Italian centres were consecutively enrolled and followed up for 12 months, with evaluations at 3, 6, 9 and 12 months. The primary objective was to describe the clinical course of IPF over 12 months of follow-up, including changes in lung function measured by % predicted forced vital capacity (FVC% predicted). RESULTS: 209 patients (82.3% male, mean age 69.54 ± 7.43 years) were enrolled. Mean FVC% predicted was relatively preserved at baseline (80.01%). The mean time between IPF diagnosis and initiation of antifibrotic therapy was 6.38 weeks; 72.3% of patients received antifibrotic therapy within the first 3 months of follow-up, and 83.9% within 12 months of follow-up. Mean FVC% predicted was 80.0% at baseline and 82.2% at 12 months, and 47.4% of patients remained stable (i.e. had no disease progression) in terms of FVC% predicted during the study. CONCLUSIONS: FIBRONET is the first prospective, real-life, observational study of patients with IPF in Italy. The short time between diagnosis and initiation of antifibrotic therapy, and the stable lung function between baseline and 12 months, suggest that early diagnosis and prompt initiation of antifibrotic therapy may preserve lung function in patients with IPF. TRIAL REGISTRATION: NCT02803580.

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.

Endocrine and metabolic assessment in adults with Langerhans cell histiocytosis.

CONTEXT: Diabetes insipidus (DI) is one of most common complications of Langerhans cell histiocytosis (LCH) but prevalence of anterior pituitary deficiencies and metabolic alterations have not been clearly defined yet. OBJECTIVES: Evaluate prevalence of endocrine and metabolic manifestations in a cohort of patients affected by Pulmonary LCH. METHODS: Observational cross-sectional study on 18 adults (7 M/11 F, 42±12years) studied for complete basal and dynamic endocrine lab tests and glucose metabolism. RESULTS: Hypothalamic-pituitary endocrine alterations were found in 9 patients: 9 had DI, 5 Growth Hormone Deficiency (GHD), 5 central hypogonadism, 3 central hypothyroidism and 1 central hypoadrenalism. Hyperprolactinemia and hypothalamic syndrome were found in 2 patients each. All these central endocrine alterations were always associated to DI. Five of the 10 MRI performed showed abnormalities. Prevalence of obesity and glucose alterations (either DM or IFG/IGT) were respectively 39% and 33%, higher than expected basing on epidemiological data on general Italian population. Multi-system-LCH without risk-organ involvement (LCH MS-RO-) seems to have slightly higher prevalence of insulin resistance, glucose alterations and metabolic syndrome than LCH with isolated lung involvement (LCH SS lung+). A papillary BRAFV600E positive thyroid carcinoma was diagnosed in one patient. CONCLUSIONS: The presence of anterior pituitary deficiencies should be systematically sought in all LCH patients with DI both at diagnosis and during the follow-up by basal and dynamic hormonal assessment. Patients with pulmonary LCH, particularly those with MS disease, have a worse metabolic profile than general population. Occurrence of papillary thyroid carcinoma has been reported.

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.

Lymphangioleiomyomatosis: what do we know and what are we looking for?

Lymphangioleiomyomatosis (LAM) is a rare disease characterised by proliferation of abnormal smooth muscle-like cells (LAM cells) leading to progressive cystic destruction of the lung, lymphatic abnormalities and abdominal tumours. It affects predominantly females and can occur sporadically or in patients with tuberous sclerosis complex. This review describes the recent progress in our understanding of the molecular pathogenesis of the disease and LAM cell biology. It also summarises current therapeutic approaches and the most promising areas of research for future therapeutic strategies.

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.

Lung function predicts lung cancer risk in smokers: a tool for targeting screening programmes.

The relationship between smoking, lung cancer and airflow obstruction is recognised but it is unclear whether the presence of minimal lung function damage constitutes an independent risk factor for the development of lung cancer. In order to identify those individuals at higher risk of lung cancer on the basis of functional impairment, we evaluated baseline pulmonary function tests of 3,806 heavy smokers undergoing annual chest computed tomography screening, and compared the forced expiratory volume in 1 s (FEV(1)) % predicted of 57 lung cancer cases and that of 3,749 subjects without cancer. We obtained odds ratios (ORs) of lung cancer and the corresponding 95% confidence intervals (CIs) using unconditional logistic regression, adjusting for age, sex, study and smoking variables. Compared with subjects with FEV(1) >or=90% pred, the OR of lung cancer was 2.45 (95% CI 1.39-4.33) for subjects with FEV(1) <90% pred and 2.90 (95% CI 1.34-6.27) for subjects with FEV(1) <70% pred. These data show that even a relatively small reduction in FEV(1) % pred is a significant predictor of increased lung cancer risk. Test screening for lung cancer using airflow obstruction with FEV(1) <90% is a strategy worth future consideration.

Salivary Streptococcus mutans and Lactobacillus sp levels in cardiac children.

This study assesses salivary conditions of 20 children with cardiac disease comparing with a control group of 15 healthy children. The results showed that there was no difference between the groups on salivary flow, buffer capacity and the level of Streptococcus mutans (Sm). The test group i.e., children with cardiac disease, showed a lower level of Lactobacillus sp. The association between the usage of antibiotics and the risk of developing caries, measuring the level of Streptococcus mutans and Lactobacillus sp., showed that children taking antibiotics frequently had a significant lower level of Lactobacillus sp (p<0.05) than healthy children. This association was not found on relation to the levels of Streptococcus mutans.