HHT is an autosomal dominant disease with an estimated prevalence of at least 1/5000 which can frequently be complicated by the presence of clinically significant arteriovenous malformations in the ...brain, lung, gastrointestinal tract and liver. HHT is under-diagnosed and families may be unaware of the available screening and treatment, leading to unnecessary stroke and life-threatening hemorrhage in children and adults.
The goal of this international HHT guidelines process was to develop evidence-informed consensus guidelines regarding the diagnosis of HHT and the prevention of HHT-related complications and treatment of symptomatic disease.
The overall guidelines process was developed using the AGREE framework, using a systematic search strategy and literature retrieval with incorporation of expert evidence in a structured consensus process where published literature was lacking. The Guidelines Working Group included experts (clinical and genetic) from eleven countries, in all aspects of HHT, guidelines methodologists, health care workers, health care administrators, HHT clinic staff, medical trainees, patient advocacy representatives and patients with HHT. The Working Group determined clinically relevant questions during the pre-conference process. The literature search was conducted using the OVID MEDLINE database, from 1966 to October 2006. The Working Group subsequently convened at the Guidelines Conference to partake in a structured consensus process using the evidence tables generated from the systematic searches.
The outcome of the conference was the generation of 33 recommendations for the diagnosis and management of HHT, with at least 80% agreement amongst the expert panel for 30 of the 33 recommendations.
Several groups have described a syndrome in which idiopathic pulmonary fibrosis (IPF) coexists with pulmonary emphysema. This comes as no surprise since both diseases are associated with a history of ...exposure to cigarette smoke. The syndrome of combined pulmonary fibrosis and emphysema (CPFE) is characterised by upper lobe emphysema and lower lobe fibrosis. Physiological testing of these patients reveals preserved lung volume indices contrasted by markedly impaired diffusion capacity. The incidence of CPFE remains unknown but several case series suggest that this subgroup may comprise up to 35% of patients with IPF. CPFE is a strong determinant of associated pulmonary hypertension (PH). In addition, CPFE has major effects on measures of physiological function, exercise capacity and prognosis, and may affect the results of pulmonary fibrosis trials. Further studies are needed to ascertain the aetiology, morbidity, mortality and management of the CPFE syndrome, with or without PH, and to evaluate novel therapeutic options in CPFE.
Patients with severe pulmonary arterial hypertension (PAH) in New York Heart Association (NYHA) functional class (FC) III/IV have a poor prognosis, despite survival benefits being demonstrated with ...intravenous epoprostenol. In this pilot study, the efficacy and safety of a triple combination therapy regimen in patients with severe PAH was investigated. Data from newly diagnosed NYHA FC III/IV PAH patients (n=19) initiated on upfront triple combination therapy (intravenous epoprostenol, bosentan and sildenafil) were collected retrospectively from a prospective registry. Significant improvements in 6-min walk distance and haemodynamics were observed after 4 months' triple combination therapy in 18 patients (p<0.01); 17 patients had improved to NYHA FC I or II. One patient was not included in the month 4 assessment (due to an emergency lung transplant in month 3). At the final evaluation (mean ± sd 32 ± 19 months), all 18 patients had sustained clinical and haemodynamic improvement. Overall survival estimates for the triple combination cohort were 100% at 1, 2 and 3 years. Expected survival calculated from the French equation was 75% (95% CI 68-82%), 60% (95% CI 50-70%) and 49% (95% CI 38-60%) at 1, 2 and 3 years, respectively. This pilot study provides preliminary evidence of the long-term benefits of upfront triple combination therapy in patients with severe PAH.
In idiopathic pulmonary fibrosis (IPF), some facts or concepts based on substantial evidence, whilst implicit for learned subspecialists, have previously been neglected and/or not explicitly ...formulated or made accessible to a wider audience. IPF is strongly associated with cigarette smoking and is predominantly a disease of ageing. However, its cause(s) remain elusive and, thus, it is one of the most challenging diseases for the development of novel effective and safe therapies. With the approval of pirfenidone for patients with mild-to-moderate IPF, an earlier diagnosis of IPF is a prerequisite for earlier treatment and, potentially, improvement of the long-term clinical outcome of this progressive and ultimately fatal disease. An earlier diagnosis may be achieved in IPF by promoting thin-slice chest high-resolution computed tomography screening of interstitial lung disease as a "by-product" of large-scale lung cancer screening strategies in smokers, but other techniques, which have been neglected in the past, are now available. Lung auscultation and early identification of "velcro" crackles has been proposed as a key component of early diagnosis of IPF. An ongoing study is exploring correlations between lung sounds on auscultation obtained using electronic stethoscopes and high-resolution computed tomography patterns.
The syndrome resulting from combined pulmonary fibrosis and emphysema has not been comprehensively described. The current authors conducted a retrospective study of 61 patients with both emphysema of ...the upper zones and diffuse parenchymal lung disease with fibrosis of the lower zones of the lungs on chest computed tomography. Patients (all smokers) included 60 males and one female, with a mean age of 65 yrs. Dyspnoea on exertion was present in all patients. Basal crackles were found in 87% and finger clubbing in 43%. Pulmonary function tests were as follows (mean+/-sd): total lung capacity 88%+/-17, forced vital capacity (FVC) 88%+/-18, forced expiratory volume in one second (FEV1) 80%+/-21 (% predicted), FEV1/FVC 69%+/-13, carbon monoxide diffusion capacity of the lung 37%+/-16 (% predicted), carbon monoxide transfer coefficient 46%+/-19. Pulmonary hypertension was present in 47% of patients at diagnosis, and 55% during follow-up. Patients were followed for a mean of 2.1+/-2.8 yrs from diagnosis. Survival was 87.5% at 2 yrs and 54.6% at 5 yrs, with a median of 6.1 yrs. The presence of pulmonary hypertension at diagnosis was a critical determinant of prognosis. The authors hereby individualise the computer tomography-defined syndrome of combined pulmonary fibrosis and emphysema characterised by subnormal spirometry, severe impairment of gas exchange, high prevalence of pulmonary hypertension, and poor survival.
Interstitial lung disease (ILD) can occur in any of the connective tissue diseases (CTD) with varying frequency and severity, and an overall long-term prognosis that is less severe than that of ...idiopathic pulmonary fibrosis (IPF). Because ILD may be the presenting manifestation of CTD and/or the dominant manifestation of CTD, clinical extra-thoracic manifestations should be systematically considered in the diagnostic approach of ILD. When present, autoantibodies strongly contribute to the recognition and classification of the CTD. Patients with clinical extrathoracic manifestations of CTD and/or autoantibodies (especially with a high titer and/or the antibody is considered "highly specific" of an autoimmune condition), but who do not fit with established international CTD criteria may be called undifferentiated CTD or "lung-dominant CTD". Although it remains to be determined which combination of symptoms and serologic tests best identify the subset of patients with clinically relevant CTD features, available evidence suggests that such patients may have distinct clinical and imaging presentation and may portend a distinct clinical course. However, autoantibodies alone when present in IPF patients do not seem to impact prognosis or management. Referral to a rheumatologist and multidisciplinary discussion may contribute to management of patients with undifferentiated CTD.
Idiopathic pulmonary fibrosis (IPF) is a progressively fibrotic disease, with no effective treatment and a median survival time of 2-5 yrs. The search for effective treatment has involved numerous ...clinical trials of investigational agents without significant success until 2011, when European approval was given for the first treatment for IPF, pirfenidone. Four key clinical trials supported the efficacy and tolerability of pirfenidone. In recently published results from two phase III randomised, double-blind, placebo-controlled, multinational trials evaluating pirfenidone (studies 004 and 006), patients with mild-to-moderate IPF were screened for eligibility using the following functional criteria: forced vital capacity (FVC) ≥50% predicted; diffusing capacity of the lung for carbon monoxide ≥35%; and 6-min walk test (6MWT) distance ≥150 m. Only study 004 met the primary end-point of change in per cent predicted FVC at week 72 (p<0.001). Pooled analysis of primary end-point data from both studies also showed that pirfenidone significantly reduced the decline in per cent predicted FVC compared to placebo (p<0.005). Evidence of beneficial effects of pirfenidone treatment was also observed with regard to several secondary end-points, including progression-free survival time, categorical FVC change, and mean change from baseline to week 72 in 6MWT distance. Pirfenidone was generally well tolerated, with the most common side-effects being gastrointestinal discomfort and photosensitivity. The pooled study results, coupled with recent data regarding the prognostic significance of changes in FVC and 6MWT, provide further evidence of a clinically meaningful treatment benefit with pirfenidone in patients with IPF.
Interstitial lung disease Cottin, Vincent
European respiratory review,
03/2013, Letnik:
22, Številka:
127
Journal Article
Recenzirano
Odprti dostop
This article reviews the most important articles published in interstitial lung disease, as reviewed during the Clinical Year in Review session at the 2012 annual European Respiratory Society ...Congress in Vienna, Austria. Since the recent international guidelines for the management of idiopathic pulmonary fibrosis (IPF), important new evidence is available. The anti-fibrotic drug pirfenidone has been recently approved in Europe. Other pharmacological agents, especially nintedanib, are still being tested. The so-called triple combination therapy, anticoagulation therapy and endothelin receptor antagonists, especially ambrisentan, are either harmful or ineffective in IPF and are not recommended as treatment. Although the clinical course of IPF is highly variable, novel tools have been developed for individual prediction of prognosis. Acute exacerbations of IPF are associated with increased mortality and may occur with higher frequency in IPF patients with associated pulmonary hypertension. Interstitial lung disease associated with connective tissue disease has been definitely established to have a better long-term survival than IPF. A subset of patients present with symptoms and/or biological autoimmune features, but do not fulfil diagnostic criteria for a given autoimmune disease; this condition is associated with a higher prevalence of nonspecific interstitial pneumonia pattern, female sex and younger age, although survival relevance is unclear.
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