The global decline in asthma death rates: can we relax now?

Whilst global asthma mortality seems to be decreasing, childhood asthma incidence is rising, and early warnings from Australia show an increase in asthma-related deaths in under-15s; this article considers whether we should view the future impact of asthma with trepidation. Age-adjusted mortality statistics for asthma have been reevaluated to provide an international standard. Comparisons across regions and time are complex, yet over the last two decades asthma mortality has clearly decreased, coinciding with a significant change in asthma management.

Is the short-term response to inhaled beta-adrenergic agonist sensitive or specific for distinguishing between asthma and COPD?

In view of the ubiquitous practice of using bronchodilator responsiveness to determine suitable patients for clinical trials, we wanted to know whether changes in FEV1 or forced vital capacity (FVC) really were useful in differentiating COPD from asthma. Pulmonary function test results from 450 patients were documented by two technicians who had been asked to select consecutive studies in which flow-volume loops showed an obstructive pattern. The respirologist responsible for the care of each patient was asked to record the clinical diagnosis from the existing outpatient chart using clinical judgment based on American Thoracic Society criteria.

Assessment of airway tone in asthma. Comparison between double lung transplant patients and healthy subjects.

We investigated the hypothesis that asthmatic patients have an increased cholinergic tone by measuring tracheobronchial cross-sectional areas during transient voluntary apnea. This allowed us to assess bronchomotor tone without the influence of changes in lung recoil or lung volume. Three groups of subjects with potentially different levels of tracheobronchial tone were studied: 14 healthy volunteers (N), 18 stable asthmatic patients (A), and 10 double lung transplant recipients (T).

Trends in asthma and chronic obstructive pulmonary disease therapy in Canada, 1985 to 1990.

Background: In the mid and late 1980s, numerous changes were recommended in the management of obstructive lung diseases. We analyzed drug sales to determine whether these recommendations have resulted in recent changes in prescription drugs used in airway management.

Methods: Data on prescription sales in Canada from 1985 to 1990 were obtained from an international pharmaceutical market research organization.

Tracheobronchial dilation during isocapnic hypoxia in conscious humans.

To assess the effects of isocapnic hypoxia on the pharynx, glottis, extrathoracic trachea (ET), intrathoracic trachea (IT), and main bronchi (MB), we measured the cross-sectional areas of these airways by acoustic reflection technique in 15 healthy volunteers. Measurements were made during tidal volume breathing while subjects were normoxic [arterial O2 saturation (SaO2) > 95%] or were made hypoxic by a rebreathing procedure. Under hypoxemic conditions, airway cross-sectional areas increased significantly at ET, IT, and MB levels (P < 0.

Changes in cross-sectional airway areas induced by methacholine, histamine, and LTC4 in asthmatic subjects.

To examine whether leukotrienes, histamine, and methacholine have different sites of bronchoconstrictor action, we studied 8 stable asthmatic subjects (mean age +/- SD, 26 +/- 5 yr) on 3 different days. On each day, a randomized challenge with LTC4, methacholine, or histamine was performed until the dose that provoked a fall of 20% in FEV1 (PC20) was obtained. Complete and partial flow-volume curves as well as area-distance profiles generated by the acoustic reflection technique (ART) at a fixed lung volume were obtained in all subjects before and after each inhalation challenge.

Erythropoietin response to acute hypoxemia in patients with chronic pulmonary disease.

Chronic hypoxemia is associated with development of secondary polycythemia. To evaluate effects of transient hypoxemia on serum EPO activity in patients with chronic lung disease, we studied six oxygen-dependent patients who underwent either a 4-h oxygen withdrawal or their routine therapy, in a randomized, blinded fashion, on two separate days. Serum EPO did not differ at baseline between study days.

Physiologic and nonphysiologic determinants of aerobic fitness in mild to moderate asthma.

We studied 27 patients (seven male, 20 female) with stable mild-to-moderate asthma to measure their level of physical fitness and to determine if a relationship existed between aerobic fitness and the degree of airway reactivity, expiratory flow rates, or the amount of habitual leisure-time physical activity. Nonspecific bronchial hyperreactivity (NSBHR) was quantified by methacholine inhalation challenge. On a separate day, exercise capacity was evaluated with incremental exercise testing to exhaustion after bronchodilator pretreatment.

The fatality-prone asthmatic patient. Follow-up study after near-fatal attacks.

We studied 12 fatality-prone patients for 18 months after they had been discharged from the hospital following life-threatening exacerbations of asthma (mean PaCO2 on admission, 97 mm Hg). Our objectives were (1) to evaluate the natural history of their disease during ambulatory care and (2) to investigate whether close follow-up might help to avert further near-fatal events. Only seven of the 12 patients consented to be enrolled in the study, which included monthly scheduled visits to the hospital and monthly telephone calls to record emergency room visits and changes in therapy.

The use of beta-agonists and the risk of death and near death from asthma.

Background: Morbidity and mortality from asthma appear to be increasing, and it has been suggested that medications used to treat asthma are contributing to this trend. We investigated a possible association between death or near death from asthma and the regular use of beta 2-agonist bronchodilators.

Methods: Using linked health insurance data bases from Saskatchewan, Canada, we conducted a matched case-control study of subjects drawn from a cohort of 12,301 patients for whom asthma medications had been prescribed between 1978 and 1987.

Clinical complexity and epidemiologic uncertainty in case-control research. Fenoterol and asthma management.

Two recent epidemiologic case-control studies suggested that fenoterol, a selective beta-adrenergic agonist, was associated with an increase in the risk of asthma death. The results of these studies were criticized because of methodologic problems in the choice and selection of control subjects; the different methods used to gather exposure data in cases and control subjects; and because of inadequate classification and adjustment for asthma severity. In response to this controversy, a new study is underway, the Saskatchewan Asthma Epidemiology Project.

Response characteristics of a dual transcutaneous oxygen/carbon dioxide monitoring system.

We tested the response characteristics of a dual transcutaneous (tc) PO2/PCO2 monitoring system in healthy subjects who breathed various gas mixtures, and we compared steady-state tc readings to simultaneous arterial blood gas analysis in 20 stable respiratory outpatients. The electrodes were simple to apply, required very little skin preparation, and had trivial signal drift. In healthy subjects, tcPCO2 lag time during CO2 rebreathing was 16.

Phrenic neural output during hypoxia in dogs: constant-flow ventilation vs. spontaneous breathing.

We studied the effects of removing cyclic pulmonary afferent neural information on respiratory pattern generation in anesthetized dogs. Phrenic neural output during spontaneous breathing (SB) was compared with that occurring during constant-flow ventilation (CFV) at several levels of eucapnic hypoxemia. Hypoxia caused an increase in both the frequency and the amplitude of the moving time average (MTA) phrenic neurogram during both SB and CFV.

Dysphagia as a manifestation of occult hypoxemia. The role of oximetry during meal times.

A 25-year-old woman with severe kyphoscoliosis reported a six-month history of increasing dysphagia to both liquids and solids. A barium swallow and esophageal motility studies showed no significant gastrointestinal abnormalities. Trials of antispasmodic agents were unsuccessful in relieving her symptoms.

Effect of a short course of prednisone in the prevention of early relapse after the emergency room treatment of acute asthma.

Background: Relapse after the treatment of acute asthma in the emergency room is common (occurring in 25 to 30 percent of cases) and is not accurately predicted by any available measurements. We studied the usefulness of prednisone in reducing this high rate of relapse.

Methods: One hundred twenty-two patients treated in the emergency room for acute exacerbations of asthma were assigned in a randomized, double-blind fashion to receive at discharge either prednisone for eight days (the dose being tapered from 40 to 0 mg per day) or matching placebo.

Impaired exercise capacity in adults with moderate scoliosis.

We measured lung function and exercise tolerance in 15 adults with moderate kyphoscoliosis (thoracic curvatures between 25 degrees and 70 degrees, mean +/- SD = 46.93 degrees +/- 14.02 degrees).

Asthma in New Zealand: implications for North America.

In the early 1980s, reports of a significant rise in asthma mortality emanated from New Zealand. Difficulties in accessing medical care, noncompliance with medication, inadequate medical management, lack of patient education, and inadequate recognition of asthma severity have been suggested as factors that may have contributed to the excess of asthma mortality. Asthma mortality has now declined significantly in New Zealand.

Emergency room care of asthmatics: a comparison between Auckland and Toronto.

We compared emergency room visits for the treatment of asthma in two large downtown teaching hospitals: one in Auckland, New Zealand and one in Toronto, Canada. We wished to determine whether the differences in asthma mortality between New Zealand and Canada were reflected in different patterns of emergency room use or physician management. Emergency room use during the past decade was enumerated in both hospitals, and charts containing the sole diagnosis of asthma were reviewed in detail for a defined study period in 1986.

Cyclosporine and chronic sarcoidosis.

Two patients with progressive sarcoidosis who had poor responses and side effects from corticosteroid therapy were treated with cyclosporine. Cyclosporine suppressed conventional markers of inflammation and there was clinical improvement in one patient, but the disease recurred when therapy was discontinued. The second patient who had diabetes mellitus developed unstable glucose metabolism when given cyclosporine.

An evaluation of flow-volume curves as a screening test for obstructive sleep apnea.

We examined flow-volume curves for their potential as screening tests for obstructive sleep apnea (OSA) in 401 patients referred for investigation of snoring. In all patients, we performed nocturnal polysomnography, maximum inspiratory and maximum expiratory flow-volume curves. The curves were examined for two features: 1) presence of flow oscillations (the "saw-tooth" sign), and 2) changes in their configuration that might suggest upper airway obstruction as documented by the expiratory/inspiratory flow ratios calculated at 50 and 75 percent of exhaled vital capacity (FR50 and FR25, respectively).

Effects of oxygen withdrawal on catecholamine release in patients on home oxygen therapy.

1. Long-term oxygen therapy in appropriate patients prolongs survival and corrects neuropsychological function. Some tests of mental function paradoxically improve during short periods of oxygen withdrawal in patients on long-term oxygen therapy, although the mechanism of this response is unknown.

Ventilatory responses to hypercapnia and hypoxia in patients with eucapnic morbid obesity before and after weight loss.

1. To examine the relationship between eucapnic morbid obesity and ventilatory responsiveness to chemical stimuli, we measured hypercapnic and hypoxic ventilatory responses in 29 patients (26 women, three men) before and 3-6 months after gastroplasty. No subject demonstrated resting awake hypercapnia and non suffered from sleep-disordered breathing.