Prognostic relevance of dynamic hyperinflation during cardiopulmonary exercise testing in adult patients with cystic fibrosis

AbstractBackgroundDynamic hyperinflation during cardiopulmonary exercise testing (CPET) in cystic fibrosis (CF) has not been well characterized, and little is known regarding its prevalence, risk factors and clinical associations.MethodsCPET data from 109 adult patients with mild-to-moderate CF was used, in this retrospective study, to characterize and determine the prevalence of dynamic hyperinflation, and evaluate its relationship with lung function and exercise tolerance, clinical symptoms, and prognosis over a two-year period.Results58% of patients responded to CPET with dynamic hyperinflation. These patients had significantly lower lung function (FEV1 66±19 versus 79±18%pred., p<0.01) and exercise tolerance (peak oxygen uptake 28.7±8.1 versus 32.9±6.1mL·kg−1·min−1, p=0.02), and experienced greater shortness of breath at peak exercise (7±3 versus 5±2 Modified Borg scale, p=0.04) compared to patients who responded without dynamic hyperinflation. Significant relationships between FEV1, FVC, FEV1/FVC, FEF25–75 and dynamic hyperinflation were shown (p<0.01; p=0.02; p<0.01; p<0.01, respectively). Dynamic hyperinflation was also significantly correlated with oxygen uptake, tidal volume, work-rate and shortness of breath at peak exercise (p=0.03; p<0.01; p<0.01; p=0.04, respectively). Responding to CPET with or without dynamic hyperinflation did not significantly predict FEV1 at 2years beyond the FEV1 at baseline (p=0.06), or increase the likelihood of experiencing a pulmonary exacerbation over a two-year period (p=0.24).ConclusionThe prevalence of dynamic hyperinflation during CPET in adult patients with mild-to-moderate CF is high, and is associated with reduced lung function and exercise tolerance, and increased exertional dyspnea. However, identifying dynamic hyperinflation during CPET had limited prognostic value for lung function and pulmonary exacerbation

International guidelines for the diagnosis and management of hereditary haemorrhagic telangiectasia

International audienceBackground 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. Objective 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. Methods 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. Results 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

Overlapping spectra of SMAD4 mutations in juvenile polyposis (JP) and JP-HHT syndrome.

Juvenile polyposis (JP) and hereditary hemorrhagic telangiectasia (HHT) are clinically distinct diseases caused by mutations in SMAD4 and BMPR1A (for JP) and endoglin and ALK1 (for HHT). Recently, a combined syndrome of JP-HHT was described that is also caused by mutations in SMAD4. Although both JP and JP-HHT are caused by SMAD4 mutations, a possible genotype:phenotype correlation was noted as all of the SMAD4 mutations in the JP-HHT patients were clustered in the COOH-terminal MH2 domain of the protein. If valid, this correlation would provide a molecular explanation for the phenotypic differences, as well as a pre-symptomatic diagnostic test to distinguish patients at risk for the overlapping but different clinical features of the disorders. In this study, we collected 19 new JP-HHT patients from which we identified 15 additional SMAD4 mutations. We also reviewed the literature for other reports of JP patients with HHT symptoms with confirmed SMAD4 mutations. Our combined results show that although the SMAD4 mutations in JP-HHT patients do show a tendency to cluster in the MH2 domain, mutations in other parts of the gene also cause the combined syndrome. Thus, any mutation in SMAD4 can cause JP-HHT. Any JP patient with a SMAD4 mutation is, therefore, at risk for the visceral manifestations of HHT and any HHT patient with SMAD4 mutation is at risk for early onset gastrointestinal cancer. In conclusion, a patient who tests positive for any SMAD4 mutation must be considered at risk for the combined syndrome of JP-HHT and monitored accordingly