Clinical significance of small airway obstruction markers in patients with asthma.

BACKGROUND: The role of small airway obstruction in the clinical expression of asthma is incompletely understood. OBJECTIVE: We tested the hypotheses that markers of small airway obstruction are associated with (i) increased asthma severity, (ii) impaired asthma control and quality of life and (iii) frequent exacerbations. METHODS: Seventy-four adults with asthma and 18 healthy control subjects underwent impulse oscillometry (IOS), multiple breath inert gas washout (MBW), body plethysmography, single-breath determination of carbon monoxide uptake and spirometry. Patients completed the six-point Asthma Control Questionnaire (ACQ-6) and standardized Asthma Quality of Life Questionnaire [AQLQ(S)]. Asthma severity was classified according to the Global Initiative for Asthma (GINA) treatment steps. RESULTS: The putative small airway obstruction markers Sacin , resistance at 5 Hz minus resistance at 20 Hz (R5-R20) and reactance area (AX) were not independently associated with asthma severity, control, quality of life or exacerbations. In contrast, markers of total (R5) and mean airway resistance of large and small airways (R20) were significantly higher in the severe asthma group compared with the mild-moderate group (0.47 vs. 0.37, P < 0.05 for R5; 0.39 vs. 0.31, P < 0.01 for R20). The strongest independent contributors to ACQ-6 score were R20 and forced expiratory volume in one second (% pred.), and the strongest independent contributors to AQLQ(S) score were R20 and forced vital capacity (% pred.). A history of one or more exacerbations within the previous year was independently associated with R20. CONCLUSIONS AND CLINICAL RELEVANCE: Previously reported markers of small airway obstruction do not appear to be independently associated with asthma disease expression. In contrast, the IOS parameter R20, a marker of mean airway resistance of both large and small airways, appears to have independent clinical significance. These observations require confirmation in prospective longitudinal studies.

Older participants are frequently excluded from Parkinson's disease research.

BACKGROUND: The exclusion of older participants from clinical research is common and limits the generalisation of research findings. We aimed to assess the current potential for older patients to participate in Parkinson's disease (PD) research. METHOD: We performed a systematic analysis of data extracted from the World Health Organization Clinical Trials Registry Platform regarding 206 actively recruiting PD research studies. Data regarding study variables and exclusion on the grounds of an upper age limit was extracted from each registry entry and subsequently used for statistical analysis. RESULTS: Exclusion by arbitrary upper age limit is common, with 101 (49%) of studies excluding participants by age and with a mean upper age limit for exclusion of 79.3 years (range 64-95 years). Exclusion by age was significantly more common in studies with an estimated enrollment of fewer than 100 participants; OR 1.92 (95%CI 1.13-3.42) P = 0.018. Rates of exclusion by age were not significantly influenced by study subject, study location, source of funding, study duration or number of centres. CONCLUSION: Exclusion of participants from PD research on the basis of an upper age limit is common and particularly problematic in smaller studies. The exclusion of older participants seriously compromises the generalisation of findings from PD research to the large numbers of elderly PD patients seen in clinical practice.

Gastroesophageal reflux in achalasia. When is reflux really reflux?

An abnormal score during 24-hr esophageal pH monitoring in achalasia may be associated either with a slow steady drift to below pH 4, or else multiple sharp dips characteristic of typical gastroesophageal reflux. To test the hypothesis that the former pattern was due to food fermentation and not reflux, samples of chewed bland food (N = 22) were incubated with saliva at 37 degrees C for 24 hr and the pH monitored (in vitro study). Further, the pH tracings of 20 patients with achalasia before operation and 12 patients after operation were studied (in vivo study). The pH of chewed food fell to a median of pH 4.0 during incubation and in seven of 22 samples fell to below pH 4. Preoperatively, four of the five patients with an abnormal pH score showed a slow steady drift, and all of these had evidence of retained food at endoscopy. Postoperatively, three of the six patients with an abnormal pH score had a slow steady drift to below pH 4. Use of pH 3 as a threshold clearly distinguished true reflux from food fermentation, since the patients with reflux all had an abnormal percentage of time below pH 3.