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PubMed1984

Fenoterol in exercise-induced asthma. Effect of dose on efficacy and duration of action.

The effectiveness of inhaled fenoterol doses of 0.4 mg and 0.8 mg in preventing exercise-induced asthma was investigated in 12 patients. Exercise-induced asthma was prevented by both doses for two hours after administration, but the effect of neither dose was significantly different from that of placebo four hours after. There was no statistically significant difference between the effects of the two fenoterol doses; and only a few patients were protected for more than two hours by the higher dose.

Adolescent↗

PubMed1984

Effect of inhaled atropine or metaproterenol in patients with chronic airway obstruction and therapeutic serum theophylline levels.

Twenty-one patients with stable chronic obstructive pulmonary disease (mean FEV1 = 0.98 L) and high-normal serum theophylline levels (15-20 micrograms/ml) were evaluated in a randomized, double-blind fashion for additional bronchodilator response to aerosolized normal saline, atropine, or metaproterenol. Patients were classified as responders (R; n = 9) or nonresponders (NR; n = 12) to inhaled isoproterenol when they were taking no medications. Atropine and metaproterenol caused a significant additional increase in FEV1 for R (p less than .05), whereas only atropine resulted in a significant increase for NR (p less than .05). For R, the increase due to atropine was significantly greater compared to metaproterenol (p less than .05). We conclude that inhaled atropine (an anticholinergic drug) may be preferable to inhaled metaproterenol (a beta-adrenergic agonist) when additional bronchodilation is needed in patients with chronic obstructive pulmonary disease and high-normal serum theophylline levels.

Aerosols↗

PubMed1984

Safety of nifedipine in subjects with bronchial asthma and COPD.

This prospective study was undertaken to evaluate the safety of nifedipine, a calcium channel blocking agent, on 60 subjects with asthma, chronic obstructive pulmonary disease (COPD), angina, and normal subjects. All subjects received nifedipine, 20 mg, sublingually. Spirometry was done pre-drug administration and every 20 minutes after for two hours. Parameters measured were forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and forced expiratory flow at 25 percent to 75 percent of total volume (FEF25-75%). Subjects with asthma and COPD were also given nifedipine 20 mg three times daily, orally for two weeks, and tested biweekly during this period. All bronchodilators, beta-blockers, and long acting nitrates were withheld for five half-lives of the drug prior to test day. There was no adverse effect on the pulmonary function. We found a statistically significant improvement (p less than 0.05) in FEV1 after nifedipine. There was no tachyphylaxis at the end of two weeks. Nifedipine is safe in patients with asthma and/or chronic bronchitis.

Adult↗

PubMed1984

Accuracy of pulmonary function tests in predicting exercise tolerance in chronic obstructive pulmonary disease.

The ability of pulmonary function tests (PFTs) to predict exercise capacity was investigated by using linear regression analysis to quantify the relationships between: (1) maximum oxygen consumption during treadmill exercise and PFT parameters; and (2) total external work performed during treadmill exercise and PFT parameters. In a group containing 11 healthy subjects, nine with mild/moderate chronic obstructive pulmonary disease (COPD) and ten with severe COPD, both maximum oxygen consumption (measured directly) and total external work (calculated indirectly from the sum of its horizontal and vertical components) correlated most strongly with indices of expiratory airflow (FEV1, FEF25-75%), less strongly with indices of ventilatory output (MVV) and resting levels of oxygen (PO2, SaO2), and weakly with indices of hyperinflation (FRC) and carbon dioxide retention (PCO2). Thus, FEV1, accounting for 56 percent and 60 percent of the observed variation in oxygen consumption and external work, respectively, can predict exercise tolerance from PFT measurements with some accuracy. If a more accurate evaluation is required, exercise testing should be prescribed.

Adolescent↗

PubMed1986

Inhalation challenge with sulfidopeptide leukotrienes in human subjects.

What is the meaning of these findings to the practicing chest physician? First, leukotrienes are potent airway constrictors; they are capable of reproducing the type of airway constriction observed in asthma. The role of leukotrienes in this regard has yet to be established, but experiments to test the importance of these agents in this setting are likely to be performed soon. Specifically, several leukotriene receptor antagonists or synthesis inhibitors have been identified and may provide the tools needed to test this crucial hypothesis. Second, the leukotrienes are unique bronchoactive agents in that the degree of hyperresponsiveness between normal and asthmatic subjects varies markedly with the bronchoconstrictor index used to assess response. When one compares normal subjects to asthmatic subjects, there is substantial overlap in leukotriene sensitivity among groups when V30-P is used as the bronchoconstrictor index. However, when the FEV1 is used as the bronchoconstrictor index, there is little overlap in sensitivity between normal and asthmatic subjects, and the separation between the two groups is even more clearly made than it is with histamine or methacholine challenge. Thus, LTD4 inhalation challenge may replace the histamine and methacholine challenges in the diagnosis of cryptic shortness of breath. Third, the differential sensitivity of various bronchoconstrictor indices in both normal and asthmatic subjects when leukotrienes are used may provide clues as to the locus of airway hyperresponsiveness in asthma. Thus, leukotrienes hold the promise of new ways to treat and diagnose asthma, as well as providing new insights into the pathobiology of the disease itself.

Administration, Intranasal↗

PubMed1986

A comparison of responses to albuterol delivered by two aerosol devices.

Nineteen outpatients with stable obstructive pulmonary disease (mean forced expiratory volume in one second [FEV1], 1.00 + 0.10 L) were evaluated for airway response to albuterol (salbutamol) administered by metered-dose inhaler and Bosch ultrasonic nebulizer (BUSN). Albuterol administered by metered-dose inhaler but not by nebulizer caused a significant increase in FEV1 and the mean forced expiratory flow over the middle half of the forced vital capacity (FEF25-75%) (p less than 0.02). Absolute increase from baseline of FEV1 and FEF25-75% was significantly greater for metered-dose inhaler (0.21 +/- 0.05 L; 0.32 +/- 0.13 L/sec) compared to ultrasonic nebulizer (0.07 +/- 0.03 L; 0.03 +/- 0.04 L/sec) (p less than 0.02). In 11 subjects (mean FEV1, 1.08 + 0.14 L), the placebo effect of inhalation of the diluent from the metered-dose inhaler (Freon) and the ultrasonic nebulizer (isotonic saline solution) was determined. Freon produced the mean increase of 1.5 percent, whereas the ultrasonic aerosol of isotonic saline solution resulted in a mean decrease of 8 percent in FEV1. Therefore, the inferior response to albuterol administered by ultrasonic nebulizer was at least in part due to the superimposed broncho-constriction occurring with ultrasonically administered saline solution. The metered-dose inhaler was more effective than the ultrasonic nebulizer for administration of albuterol in stable obstructive pulmonary disease, and the latter device is not recommended. A specific ultrasonic nebulizer should be prescribed only if its superiority to a metered-dose inhaler can be objectively documented.

Aerosols↗

PubMed1988

Spirometry and chest wall dimensions in achondroplasia.

Standard values for pulmonary function in short-limbed dwarfism are not available. Therefore, chest diameters and expiratory spirograms were measured in 58 female and 44 male subjects between 7 and 60 years of age with achondroplasia, the most common form of dwarfism. Standing height in adults was 49.6 +/- 3.2 (SD) inches with a sitting/standing height ratio of 0.66 (normal 0.52-0.53). Despite extremely short stature, only AP chest diameters in males were smaller than control subjects of similar age. The following equations were derived for forced vital capacity (FVC): males (under 25 years), FVC(L) = -3.56 + 0.162 X sitting height (in) + 0.067 X age (yrs); males (over 25 years), FVC(L) = -0.73 + 0.162 X sitting height (in) -0.047 X age (yrs); females (under 20 years), FVC(L) = -3.56 + 0.150 X sitting height (in) + 0.067 X age (yrs); females (over 20 years), FVC(L) = -1.92 + 0.150 X sitting height (in) -0.016 X age (years). Similar prediction equations were derived for FEV1 and FEF25-75%: FEV1/FVC % was 84.2 (+/- 6.5) for females and 88.0 (+/- 6.5) for males. We also compared the observed FVC measurements to values calculated using standing heights derived from the subject's sitting height, assuming a normal body proportion. The observed vital capacity in achondroplasia was only 67.6 (+/- 19.2) percent of that predicted for normally proportioned females and 72.4 (+/- 13.6) percent for males, suggesting reduced vital capacity in achondroplasia, due to reduced chest wall compliance or abnormal lung growth.

Achondroplasia↗

PubMed1988

Airway hyperreactivity in cystic fibrosis. Clinical correlates and possible effects on the course of the disease.

To evaluate whether increased airway reactivity affected the course of patients with cystic fibrosis (CF), we categorized 40 CF patients as to methacholine sensitivity and then evaluated their disease activity and natural history. Twenty methacholine reactors had more severe lung disease (lower S-K clinical scores and more impairment of pulmonary function) than did 16 nonreactive patients, and acute bronchodilator response was greater in the methacholine reactors. Thirty-four patients were followed prospectively over a 17- to 24-month period. Among 19 methacholine reactors, there were more pulmonary exacerbations and a more rapid decline in FEV1. In general, increased obstruction was associated with increased reactivity. Although the data are subject to differing interpretations, they are consistent with the hypothesis that in patients with CF, airway hyperreactivity occurs secondary to bronchial damage, age, is associated with more rapid pulmonary deterioration, and is an unfavorable prognostic finding.

Adolescent↗

PubMed1989

Role of inhalation challenge testing in the diagnosis of isocyanate-induced asthma.

Results of isocyanate challenge tests performed on 63 workers referred with a diagnosis of probable isocyanate asthma between 1974 and 1988 were reviewed. Thirty (48 percent) had an acute episode of asthma with a greater than 20 percent decline in FEV1 following subirritant exposure to isocyanates. No difference in the frequency or type of respiratory complaints between isocyanate reactors and nonreactors was found. No differences in lung function results were present when comparing smoking and ex-smoking reactors and nonreactors. In never-smokers with complaints consistent with isocyanate-induced asthma, the presence of obstructive lung disease increased the likelihood that isocyanate-induced asthma was present. Bronchial responsiveness to methacholine occurred in nearly all isocyanate reactors but predicted isocyanate-induced asthma in only 68 percent of the workers. In nearly all cases of challenge-confirmed toluene diisocyanate (TDI)-induced asthma, a 15-min exposure to 20 ppb of the commercial TDI mixture (80:20 2,4:2,6) provoked asthma. Conversely, in the absence of an asthmatic response following exposure to this dose for this duration, a second exposure at this concentration for a longer time would be reasonable to confirm the absence of isocyanate-induced asthma. Among workers employed in the production of polyurethane foam and confirmed to have TDI-induced asthma by inhalation challenge to the different TDI isomers, there appeared to be increased airway reactivity to the 2,6 isomer. This may have relevance to the frequency and intensity of respiratory symptoms that workers with TDI-induced asthma develop in differing industrial settings.

Adult↗

PubMed1990

Bronchodilator effect of inhaled formoterol vs salbutamol over 12 hours.

The bronchodilator effects were compared in 16 stable asthma patients for 12 hours after either 12 micrograms formoterol or 200 micrograms salbutamol from a metered-dose aerosol in a randomized, double-blind, crossover study. The FEV1 measured before 1, 2, 4, 6, 8, 10 and 12 hours after administration was used as the parameter. From 2 hours onwards after dosage, the bronchodilator effect of formoterol was statistically significantly greater than that of salbutamol. The effect of formoterol lasted longer, and even after 12 hours, the FEV1 was still 20 percent above the baseline value. This is clinically significant and offers new possibilities for treatment of the so-called "morning dip." Both agents were well tolerated.

Adrenergic beta-Agonists↗

PubMed1990

Acute respiratory and cardiovascular effects of inhaled ketanserin in chronic obstructive pulmonary disease. A comparative study with intravenously administered ketanserin.

In a double-blind, crossover study, nebulized ketanserin, a 5-HT2 receptor antagonist, and a placebo were given to eight patients with moderate to severe nonasthmatic COPD. Intravenous ketanserin had rapid onset of action and induced a longer lasting bronchial response than inhaled ketanserin. These results confirm that ketanserin acts as a mild bronchodilator in patients with COPD and demonstrate that the inhaled route has no advantage over the intravenous route in terms of effectiveness. Thus, 5-HT may play a role in bronchomotor tone, at least in patients with chronic airway obstruction.

Administration, Inhalation↗

PubMed1990

The assessment of major airway function in a ventilator-dependent patient with tracheomalacia.

A 60-pack-year smoker presented with cough, dyspnea and orthopnea of three months' duration. Spirometry revealed severe reduction in maximal expiratory flow; CT of the chest and bronchoscopy demonstrated expiratory collapse of a mid-tracheal segment, and a presumptive diagnosis of tracheomalacia was made. A right lateral thoracotomy was performed to resect the unstable segment and improve maximal expiratory flow. Diffuse major airway disease with absence of cartilaginous rings from the thoracic inlet to the mainstem bronchi was encountered. The trachea and mainstem bronchi were stented externally. A high resistance to airflow and absence of expiratory flow limitation were present, suggesting a fixed rather than variable intrathoracic obstruction of major airways. This case illustrates some potential pitfalls in preoperative assessment of patients with tracheomalacia. Recordings of airway pressure and flow during mechanical ventilation are useful in distinguishing between fixed and variable intrathoracic obstruction and may complement tests of airway anatomy.

Airway Resistance↗

PubMed1990

Effect of PAF-acether inhalation on nonspecific bronchial reactivity and adrenergic response in normal and asthmatic subjects.

Bronchial hyperreactivity, although recognized as a hallmark of asthma, is not totally understood. Mast cell-derived mediators, including histamine, have been shown to cause immediate bronchoconstriction, but until recently, no single mediator has been shown to induce prolonged changes in airway reactivity. Recent reports indicate PAF-acether (PAF) can induce increased nonspecific bronchial reactivity in normal subjects but not in asthmatics. We sought to elucidate the role of PAF in airway hyperreactivity by comparing the effect of inhaled PAF on methacholine and isoproterenol airway responsiveness in six nonasthmatic and six asthmatic subjects. Neither nonspecific airway reactivity nor isoproterenol responsiveness was changed following PAF inhalation in the nonasthmatic subjects in the six days following PAF. Asthmatics had increased airway responsiveness to methacholine at two hours post-PAF, which did not persist. Responsiveness to isoproterenol did not change in the asthmatic subjects. Additional evaluation of the role of PAF in causing changes in airway reactivity is warranted.

Adult↗

PubMed1990

Pulmonary functional impairment associated with pleural asbestos disease. Circumscribed and diffuse thickening.

To define the pulmonary functional impairment associated with pleural asbestos signs (PAS), we compared 738 men with only circumscribed (plaques) or diffuse pleural thickening on chest roentgenograms but no irregular opacities by ILO pneumoconiosis criteria (1980) with 738 age-matched asbestos-exposed men without any roentgenographic signs and with 228 men unexposed to asbestos. All men were white. Spirometry and total thoracic gas volumes (TGV) were measured and expressed as percentage of predicted of white Michigan men who have been modeled for spirometric values thereby adjusting for height, age, and in current and ex-smokers for duration of smoking. Asbestos-exposed men who never smoked had reduced FEF75-85 (p less than 0.01) and increased TGV (p less than .0001) as compared with unexposed men. The 155 men with PAS who had never smoked had reduced flows (p less than .0001), FVC (p less than 0.0056), and TGV (p less than .0001) when compared with 155 age-matched asbestos-exposed men. The 325 asbestos-exposed current smokers with normal chest roentgenograms compared with unexposed smokers had reduced expiratory airflows (p less than 0.0001), reduced FEV1 (p less than 0.004), and increased TGV (p less than 0.0001). The 325 current smokers with PAS had additional air trapping that further reduced vital capacity. Thus, PAS were associated with significant pulmonary dysfunction in men who never smoked, and current and ex-smokers had additional dysfunction even after adjustment for duration of smoking.

Asbestosis↗

PubMed2003

Methods for "indirect" challenge tests including exercise, eucapnic voluntary hyperpnea, and hypertonic aerosols.

Bronchial provocation tests that use stimuli that act indirectly to cause airway narrowing have a high specificity for identifying people with active asthma who have the potential to respond to treatment with antiinflammatory drugs. The first test to be developed was exercise and it was used to assess the efficacy of drugs such as sodium cromoglycate. Eucapnic voluntary hyperpnea was developed later, as a surrogate test for exercise. Hypertonic aerosols were introduced to mimic the dehydrating effects of evaporative water loss that occurs during hyperpnea. A wet aerosol of 4.5% saline or a dry powder formulation of mannitol is used. At present the indirect challenge tests are becoming increasingly recognised as appropriate for monitoring treatment with inhaled steroids. Indirect tests identify those with potential for exercise-induced bronchoconstriction, an important problem for some occupations, such as the defence forces, fire fighters and the police force and for some athletic activities. The advantage in using an indirect challenges, over a direct challenge with a single pharmacological agonist, is that a positive response indicates that inflammatory cells and their mediators (prostaglandins, leukotrienes and histamine) are present in the airways in sufficient numbers and concentration to indicate that asthma is active at the time of testing. The corollary to this is that a negative test in a known asthmatic indicates good control or mild disease. Another advantage is that healthy subjects do not have significant airway narrowing to indirect challenge tests. The protocols used for challenge with indirectly acting stimuli are presented in detail.

Adult↗

PubMed1986

Urinary arginine-vasopressin (AVP) excretion in cystic fibrosis (CF).

Free water handling is impaired in chronic obstructive lung disease (COLD). We studied the role of AVP in this mechanism with a sensitive urinary AVP radioimmunoassay (RIA) in 13 patients with CF. The mean age was 14.7 +/- 1.27 SE years. The control group was age and sex matched. While the 24-hour urine volume was not significant different in both groups, urine osmolality was higher in CF (788 mosmol/kg +/- 182 SE vs. 622 mosmol/kg +/- 218 SE; p = 0.05). The 24-hour urinary AVP excretion in CF patients was found to be significantly elevated (174 ng/day +/- 99 SE vs. 74 ng/day +/- 48 SE; p = 0.01). This difference becomes even greater if these values are corrected for body weight (4.4 ng/(kg X day) +/- 2.1 SE vs. 1.5 ng/(kg X day) +/- 0.9 SE; p = 0.005). Lung function studies were available in 8 patients. We used a body plethysmograph to measure FEV1 (1 sec forced expiratory volume) and MEF25 (forced expiratory flow at 25% of vital capacity) as sensitive indices of airway obstruction. There was a significant negative correlation between urinary AVP excretion and MEF25 (r = .76) and FEV1 (r = .65): the more pronounced the airway obstruction the higher the AVP excretion. We conclude that AVP plays a major role in the impaired water handling in COLD. Increased AVP secretion is already present under clinically stable conditions and is dependent on the degree of airway obstruction. In treating those patients one has to be aware of the possibility of water intoxication.

Adolescent↗

PubMed1995

Impairment of lung volumes and respiratory muscle strength in adult patients with growth hormone deficiency.

Little is known of the respiratory function in patients with growth hormone (GH) deficiency. The aim of the present study was to evaluate lung volumes and respiratory muscle strength in patients diagnosed as GH deficient in childhood. Ten patients diagnosed as GH deficient in childhood and ten healthy subjects entered the study. For each subject the evaluation of respiratory function followed the same standard approach, consisting of respiratory muscle strength assessment, recording of flow-volume curves, measurement of static lung volumes and lung diffusing capacity. Both maximal inspiratory and expiratory mouth pressures were decreased in GH deficiency. Vital capacity, N2 functional residual capacity and total lung capacity were significantly reduced when compared to healthy subjects. Conversely, the residual volume and diffusing lung capacity to CO did not show any significant change. No significant change of percentage forced expiratory volume in 1 s/forced vital capacity ratio was observed. The decrease of respiratory mouth pressures was not correlated to the decrease of lung volumes. In conclusion, the results of this study show that adult patients affected with childhood onset GH deficiency suffer from impairment of ventilatory function and a decrease of respiratory muscle pressures, probably due to reduction of respiratory muscle strength.

Adult↗

PubMed1986

Improvement of ventilatory function by spa therapy in patients with intractable asthma.

Twenty-five patients with intractable asthma had swimming training in a hot spring pool for 3 months. The subjects were divided into three groups according to their clinical symptoms and ages. Changes of ventilatory function during swimming training were observed in in each group. The ventilatory function test revealed that free swimming training in a hot spring pool for 30 min did not induce bronchoconstriction in any of the groups. The values of ventilatory parameters such as FEV 1.0%, %PEFR, %V50 and %V25 were improved after the 3-month swimming training. The improvement of ventilatory parameters, especially %MMF, %V50 and %V25, by the training was most remarkable in the type II asthma group. The percent increase in %MMF, %V50 and %V25 was highest in patients more than 61 years of age, and higher in patients aged 40 to 60 years than in younger patients.

Adolescent↗