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Acid-Base Disorders in Patients with Chronic Obstructive Pulmonary Disease: A Pathophysiological Review

The authors describe the pathophysiological mechanisms leading to development of acidosis in patients with chronic obstructive pulmonary disease and its deleterious effects on outcome and mortality rate.

Renal compensatory adjustments consequent to acidosis are also described in detail with emphasis on differences between acute and chronic respiratory acidosis. Mixed acid-base disturbances due to comorbidity and side effects of some drugs in these patients are also examined, and practical considerations for a correct diagnosis are provided.

Are reference equations for spirometry an appropriate criterion for diagnosing disease and predicting prognosis?

In the last few years, there has been considerable debate on the use of threshold criteria for the diagnosis of obstructive lung disease based on FEV(1) and FEV(1)/FVC ratio. It has been argued that a fixed ratio and fixed percentage criterion result in misclassification.

The author argues that this critique is based on a false presumption about the validity of reference equations as a criterion for normality. The flaw lies in the methods used to derive reference equations, which involve arbitrary and circular criteria for exclusion of some members of the population, use potentially non-representative reference populations and include predictive variables that are really risk factors for disease or for adverse outcomes of disease. The author argues for a new interpretative approach for the use of lung function data in clinical practice based on prognostic equations analogous to the Framingham cardiovascular risk factor equations.

These interpretative equations should be based on data from cohort studies and randomised controlled trials, rather than cross-sectional studies, and if properly formulated, will prove to be valuable aids to clinical decision making.

Nonspecific interstitial pneumonia: a study of 6 patients with progressive disease.

This study describes the clinical presentations and histology of surgical biopsy-proven nonspecific interstitial pneumonia (NSIP) in 6 patients with clinical and radiologic progression, resulting in the need for rebiopsy or lung transplantation.

The majority of patients were middle-aged women (F/M=5) with shortness of breath, dyspnea on exertion, and dry cough. Three had evidence of autoimmune disease/phenomena. High-resolution computerized tomographic scans revealed bilateral ground-glass infiltrates without honeycomb change in 4 of 6 cases; over time (16 to 115 mo), 5 of the 6 cases developed subpleural honeycomb change. Histologic examination of the initial biopsy showed fibrotic variant NSIP in 5 cases and cellular variant NSIP in 1 case. At repeat biopsy and/or transplantation, the 5 cases of fibrotic NSIP showed morphologic features of usual interstitial pneumonia, whereas the cellular case showed fibrotic variant NSIP.

The potential pathophysiologic explanation for such a change is discussed.

Lansoprazole for children with poorly controlled asthma: a randomized controlled trial.

CONTEXT: Asymptomatic gastroesophageal reflux (GER) is prevalent in children with asthma. Untreated GER has been postulated to be a cause of inadequate asthma control in children despite inhaled corticosteroid treatment, but it is not known whether treatment with proton pump inhibitors improves asthma control.

OBJECTIVE: To determine whether lansoprazole is effective in reducing asthma symptoms in children without overt GER.

DESIGN, SETTING, AND PARTICIPANTS: The Study of Acid Reflux in Children With Asthma, a randomized, masked, placebo-controlled, parallel clinical trial that compared lansoprazole with placebo in children with poor asthma control who were receiving inhaled corticosteroid treatment. Three hundred six participants enrolled from April 2007 to September 2010 at 19 US academic clinical centers were followed up for 24 weeks. A subgroup had an esophageal pH study before randomization.

INTERVENTION: Participating children were randomly assigned to receive either lansoprazole, 15 mg/d if weighing less than 30 kg or 30 mg/d if weighing 30 kg or more (n = 149), or placebo (n = 157).

MAIN OUTCOME MEASURES: The primary outcome measure was change in Asthma Control Questionnaire (ACQ) score (range, 0-6; a 0.5-unit change is considered clinically meaningful). Secondary outcome measures included lung function measures, asthma-related quality of life, and episodes of poor asthma control.

RESULTS: The mean age was 11 years (SD, 3 years). The mean difference in change (lansoprazole minus placebo) in the ACQ score was 0.2 units (95% CI, 0.0-0.3 units). There were no statistically significant differences in the mean difference in change for the secondary outcomes of forced expiratory volume in the first second (0.0 L; 95% CI, -0.1 to 0.1 L), asthma-related quality of life (-0.1; 95% CI, -0.3 to 0.1), or rate of episodes of poor asthma control (relative risk, 1.2; 95% CI, 0.9-1.5). Among the 115 children with esophageal pH studies, the prevalence of GER was 43%. In the subgroup with a positive pH study, no treatment effect for lansoprazole vs placebo was observed for any asthma outcome. Children treated with lansoprazole reported more respiratory infections (relative risk, 1.3 [95% CI, 1.1-1.6]).

CONCLUSION: In this trial of children with poorly controlled asthma without symptoms of GER who were using inhaled corticosteroids, the addition of lansoprazole, compared with placebo, improved neither symptoms nor lung function but was associated with increased adverse events.

TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00442013.

Respiratory diseases and muscle dysfunction.

Many respiratory diseases lead to impaired function of skeletal muscles, influencing quality of life and patient survival. Dysfunction of both respiratory and limb muscles in chronic obstructive pulmonary disease has been studied in depth, and seems to be caused by the complex interaction of general (inflammation, impaired gas exchange, malnutrition, comorbidity, drugs) and local factors (changes in respiratory mechanics and muscle activity, and molecular events).

Some of these factors are also present in cystic fibrosis and asthma. In obstructive sleep apnea syndrome, repeated exposure to hypoxia and the absence of reparative rest are believed to be the main causes of muscle dysfunction. Deconditioning appears to be crucial for the functional impairment observed in scoliosis. Finally, cachexia seems to be the main mechanism of muscle dysfunction in advanced lung cancer.

A multidimensional therapeutic approach is recommended, including pulmonary rehabilitation, an adequate level of physical activity, ventilatory support and nutritional interventions.

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