Impaired Carbon Monoxide Diffusing Capacity is the strongest lung function predictor of decline in 12 minute-walking distance in COPD; a 5-year follow-up study.

BACKGROUND: The purpose of this study was to evaluate the longitudinal relationship between functional exercise capacity, assessed through standardized 12-minute walk test (12MWT), and various lung function parameters obtained using spirometry, body plethysmography and diffusing capacity (DLco) measurements in patients with COPD. METHODS: Spirometry, body plethysmography and DLco-measurements were performed at baseline in 84 subjects with moderate to very severe COPD and at follow-up visit (n = 34) after 5 years. Functional exercise capacity was determined using standardized 12MWT. RESULTS: Patients were characterized at baseline by FEV1 of 1.2 ± 0.4 L (41 ± 13% predicted), RV of 3.4 ± 1.0 L (187 ± 58% predicted) and DLco of 3.8 ± 1.2 mmol/min/kPa (51 ± 16% predicted). A decrease of 12MWD was found between baseline and follow-up (928 ± 193 m vs. 789 ± 273 m, p < 0.001). DLco and 12MWD at baseline were the only independent predictors of 12MWD at follow-up in a multiple logistic regression model that also included all other lung function parameters, gender, age and BMI. Decline in 12MWD was mainly explained by deterioration in DLco. Furthermore, DLco value at baseline had the highest explanatory value for the loss in 12MWD after 5 years (R2 = 0.18, p = 0.009). CONCLUSIONS: In a 5-year longitudinal study, DLco-measurements at baseline were the most important predictors of declining exercise capacity in COPD patients. These results suggest that integration of DLco in the clinical workup provides a more comprehensive assessment in patients with COPD.

Early initiation of enzyme replacement therapy for the mucopolysaccharidoses.

The mucopolysaccharidoses (MPS), a group of rare genetic disorders caused by defects in glycosaminoglycan (GAG) catabolism, are progressive, multi-systemic diseases with a high burden of morbidity. Enzyme replacement therapy (ERT) is available for MPS I, II, and VI, and may improve walking ability, endurance, and pulmonary function as evidenced by data from pivotal trials and extension studies. Despite these demonstrable benefits, cardiac valve disease, joint disease, and skeletal disease, all of which cause significant morbidity, do not generally improve with ERT if pathological changes are already established. Airway disease improves, but usually does not normalize. These limitations can be well understood by considering the varied functions of GAG in the body. Disruption of GAG catabolism has far-reaching effects due to the triggering of secondary pathogenic cascades. It appears that many of the consequences of these secondary pathogenic events, while they may improve on treatment, cannot be fully corrected even with long-term exposure to enzyme, thereby supporting the treatment of patients with MPS before the onset of clinical disease. This review examines the data from clinical trials and other studies in human patients to explore the limits of ERT as currently used, then discusses the pathophysiology, fetal tissue studies, animal studies, and sibling reports to explore the question of how early to treat an MPS patient with a firm diagnosis. The review is followed by an expert opinion on the rationale for and the benefits of early treatment.

The prognostic value of fixed time and self-paced walking tests in patients diagnosed with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic fibrosing interstitial pneumonia that has an unknown etiology. The natural history of the disease is characterized by a progressive decline in pulmonary function and overall health and well-being. The median survival time is between 2-3 years; however, the disease course is variable and unpredictable. The twelve-minute walking test (12MWT) and six-minute walking test (6MWT) are two fixed time tests that are commonly used in clinical practice. Our short and clinically oriented narrative review attempted to summarize current evidence supporting the use of fixed time, self-paced walking tests in predicting the outcome of patients diagnosed with IPF. A number of studies have justified that the 6MWT is a simple, cost-effective, well documented, fixed time, and self-paced walking test which is a valid and reliable measure of disease status and can also be used as a prognostic tool in patients with IPF. However, there is a need for dedicated and validated reference equations for this population of patients. It is also necessary to fill the knowledge gap about the role of the 12MWT. We hypothesize that it would be useful in evaluating patients that are in the early stages of the disease.

Comparison of laboratory- and field-based exercise tests for COPD: a systematic review.

Exercise tests are often used to evaluate the functional status of patients with COPD. However, to the best of our knowledge, a comprehensive systematic comparison of these tests has not been performed. We systematically reviewed studies reporting the repeatability and/or reproducibility of these tests, and studies comparing their sensitivity to therapeutic intervention. A systematic review identified primary manuscripts in English reporting relevant data on the following exercise tests: 6-minute walk test (6MWT) and 12-minute walk test, incremental and endurance shuttle walk tests (ISWT and ESWT, respectively), incremental and endurance cycle ergometer tests, and incremental and endurance treadmill tests. We identified 71 relevant studies. Good repeatability (for the 6MWT and ESWT) and reproducibility (for the 6MWT, 12-minute walk test, ISWT, ESWT, and incremental cycle ergometer test) were reported by most studies assessing these tests, providing patients were familiarized with them beforehand. The 6MWT, ISWT, and particularly the ESWT were reported to be sensitive to therapeutic intervention. Protocol variations (eg, track layout or supplemental oxygen use) affected performance significantly in several studies. This review shows that while the validity of several tests has been established, for others further study is required. Future work will assess the link between these tests, physiological mechanisms, and patient-reported measures.