Effect of aminophylline on exercise performance in patients with irreversible airway obstruction

Thirteen clinically stable male patients aged 63 +/- 3 years with irreversible airway disease were given aminophylline and placebo in a randomized crossover fashion on two consecutive days while receiving beta-agonists. During incremental exercise the maximal heart rate (139.0 +/- 22.1 vs 128.0 +/- 16.4 beats per minute) and minute ventilation (41.9 +/- 6.9 vs 38.1 +/- 8.2 L/min) were significantly higher and the arterial carbon dioxide pressure (34.6 +/- 5.0 vs 38.6 +/- 7.7 mm Hg) was significantly lower during aminophylline administration than during placebo administration. However, spirometric findings, maximal inspiratory pressures, maximal oxygen consumption, work rate, and arterial oxygen pressure were similar on both regimens. We concluded that the major effect of aminophylline is to increase ventilatory drive in patients with irreversible airway obstruction. Unless an objective change in spirometric data or exercise capacity can be documented, we believe that aminophylline therapy is not warranted in these patients.     

Improvement of “irreversible” airway obstruction by thiazinamium (Multergan®)

Thiazinamium (Multergan®, 50 mg intramuscularly) improved lung function (forced expiratory volume in one second [FEV_1.0]; forced vital capacity [FVC]) within one hour after injection in 11 men (average age 66.4 years) with chronic cough, phlegm, and dyspnea, and with severe ventilatory function loss (average FEV_1.0, 42.5% of predicted values; average FVC, 64.6%) due to prolonged exposure (≥28 years) to dust of soft hemp in industry. The increase of FEV_1.0 and of FVC after thiazinamium was significantly greater than that observed after isoproterenol inhalation in the same subjects. The acute effect of thiazinamium, which lasted at least six hours, was maintained over a one-month period of daily injections. Oral administration of 200 mg thiazinamium had little effect on FEV_1.0 and FVC. The results suggest that "irreversible" airway obstruction may be more amenable to drug treatment than is often thought.     

Cardiovascular response to acute airway obstruction and hypoxia

We wished to evaluate the role of hypoxia in the production of cardiovascular manifestations of acute airway obstruction. We monitored blood pressure, electrocardiogram, and radionuclide ejection fraction in 14 healthy volunteers on exposure to four experimental conditions: expiratory resistive loading while breathing room air (RAL), expiratory resistive loading while hypoxic (HL), hypoxia alone (H), and expiratory resistive loading while voluntarily hyperventilating in a pattern similar to HL trials (VL). Mean respiratory-related oscillation in systolic blood pressure (pulsus paradoxus) increased significantly under each experimental condition compared with those at baseline (2 +/- 2.3 mm Hg): for RAL, 21 +/- 8.4 mm Hg; for HL, 34 +/- 16.3 mm Hg; for H, 10 +/- 5.4 mm Hg; for VL 26 +/- 13.4 mm Hg. Pulsus paradoxus was significantly greater under conditions of moderate hypoxia (saturation, 80%) than of mild hypoxia (saturation, 90%). Electrocardiographic changes were more marked under HL and H conditions than under RAL and VL conditions. HL induced changes in blood pressure and frontal QRS axis that were qualitatively similar to those seen in naturally occurring asthma. Radionuclide ejection fraction showed no dramatic change with any experimental condition. We conclude that hypoxia magnifies the cardiovascular changes induced by acute expiratory resistive loads and may contribute to the degree of pulsus paradoxus seen in severe asthma.     

Evaluation of bronchodilator response in patients with airway obstruction.

The aim of this study was to define the most useful index of expressing bronchodilator response and to distinguish between asthma and COPD. A prospective study was carried out of bronchodilator response in 142 asthmatics and 58 COPD patients in a university hospital. Reversibility was expressed as: 1. absolute change (delta abs); 2. % of initial (delta %init); 3. % of predicted (delta %pred) and 4. % of maximum possible response (delta %max). Dependence on forced expirations volume in 1 sec (FEV1) as % of predicted and sensitivity and specificity for diagnosis of asthma were established. A relationship between delta abs and initial FEV1 was not found in asthma (delta abs vs. % initial FEV1. r = 0.07) or COPD (r = 0.02). delta %pred did not show a correlation in asthma (r = 0.10) or COPD (r = 0.06). delta %init was dependent on the baseline value in asthma (r = 0.38, P < or = 0.001) but not in COPD (r = 0.18, P = n.s.). delta max was dependent in both. The combination of best sensitivity and specificity to separate asthma and COPD was obtained with delta abs (70.4 or 70.6%). The worst specificity for asthma diagnosis was obtained with delta %init (50%). The best likelihood ratios were obtained with delta abs and delta %pred and the worst likelihood ratio with delta %init. delta %init is not recommended as an index for differential diagnosis between asthma and COPD; 2) delta %init overscores bronchodilator response in patients with low FEV1. The independence of each bronchodilator response index should be verified in clinical trials for each selected sample.     

Bronchodilator response in chronic obstructive pulmonary disease

We measured response to 250 micrograms isoproterenol in 985 patients with COPD who were carefully studied and followed closely for nearly 3 yr. Response was quantitated in relative (% increase in FEV1) and absolute (change in FEV1 as a % predicted normal) terms. Patients were told to abstain from bronchodilator for 6 h before testing, and responses were larger in those who said they had done this. Responses were not related to blood theophylline concentrations. In patients who had abstained for 6 h, response averaged 15% of the baseline FEV1 or 5% of the predicted normal FEV1. Relative response was inversely proportional to baseline FEV1, whereas absolute response was directly related to baseline FEV1. Responses were positively related to symptomatic wheezing and exercise capacity, and negatively to smoking history, but these features accounted for little of the observed variation in response. Patients with large relative and absolute responses demonstrated increased variability of FEV1 with time and a decreased annual rate of decline of FEV1. There was little change in response with time, and the change observed could probably be explained by a gradual decrease in FEV1. However, time-related interindividual and intraindividual variations of response were large and impossible to separate from random variations of FEV1.     

Sensitivity of volume of isoflow in the detection of mild airway obstruction.

The relative sensitivity of volume of isoflow test for detecting obstruction was compared to that of other tests, including flow at 60 per cent of total lung capacity, closing volumes, and frequency dependence of dynamic lung compliance. The volume of isoflow was measured in a waterless spirometer after 3 vital capacity inspirations of a mixture of 80 per cent oxygen. We studied 22 asymptomatic, healthy smokers (18 men and 4 women, 32.5 +/- 7.2 years of age, who smoked 5 to 20 pack-years). Thirteen smokers had an abnormal volume of isoflow, yet only 4 had an abnormal flow at 60 per cent of total lung capacity and 2 had an abnormal closing volume. Abnormal frequency dependence of dynamic lung compliance was demonstrated in 3 of 7 smokers tested with an abnormal volume of isoflow; none was detected in 7 smokers tested with normal volume of isoflow. Static pressure-volume curves and diffusing capacity were normal in all smokers with an abnormal volume of isoflow, and after bronchodilator inhalation, volume of isoflow improved in one half of the subjects. These results suggest reversible, intrinsic airway obstruction in the presence of normal flow at 60 per cent of total lung capacity and closing volume. Furthermore, volume of isoflow was a more sensitive test that flow at 60 per cent total lung capacity, closing volume, or frequency dependence of dynamic lung compliance.     

Central airway obstruction

Central airway obstruction is a problem facing all medical and surgical subspecialists caring for patients with chest diseases. The incidence of this disorder appears to be rising because of the epidemic of lung cancer; however, benign causes of central airway obstruction are being seen more frequently as well. The morbidity is significant and if left untreated, death from suffocation is a frequent outcome. Management of these patients is difficult, but therapeutic and diagnostic tools are now available that are beneficial to most patients and almost all airway obstruction can be relieved expeditiously. This review examines current approaches in the workup and treatment of patients suffering from airway impairment. Although large, randomized, comparative studies are not available, data show significant improvement in patient outcomes and quality of life with treatment of central airway obstruction. Clearly, more studies assessing the relative utility of specific airway interventions and their impact on morbidity and mortality are needed. Currently, the most comprehensive approach can be offered at centers with expertise in the management of complex airway disorders and availability of all endoscopic and surgical options.     

Bronchodilator response during acute viral bronchiolitis in infancy

Bronchodilator responsiveness was assessed by measuring specific respiratory conductance before and after inhalation of aerosolized bronchodilator in 50 infants who had acute bronchiolitis due to respiratory syncytial virus infection. Thirty per cent of the infants showed an improvement in specific conductance. Responders could not be differentiated from nonresponders by family histories of atopy, eosinophil counts, or immunoglobulin levels in blood and nasal secretions. Eighty-three per cent of the families and 54% of the mothers of the infants were smokers. Babies of smoking mothers had lower specific conductances than did those of nonsmoking mothers but showed no differences in bronchodilator response. The clinical significance of this bronchodilator-responsive sub-group has yet to be defined.     

Irreversible airway obstruction in asthma

Asthma is generally characterized by fully reversible airway obstruction. However, a significant proportion of asthma patients demonstrate an incomplete reversibility of airway obstruction (IRAO) despite optimal treatment and the absence of a significant smoking history. Such partially irreversible airway obstruction may be due to residual airway inflammation, particularly of the eosinophilic type, and structural changes. Risks factors for IRAO include reduced pulmonary function early in life, frequent exacerbations, smoking, continuing exposure to a sensitizing agent, and adult-onset asthma. IRAO is associated with increased disease severity and increased asthma-related morbidity and mortality. Optimal asthma control, including prevention of asthma exacerbations, smoking avoidance, and sufficient anti-inflammatory therapy, should be implemented in an effort to avoid an accelerated decline in lung function and the development or worsening of IRAO.     

Diurnal rhythms in airway obstruction

Diurnal patterns of variation in peak expiratory flow rate were studied in patients with all types of airway obstruction. Most regular patterns fall into one of two types: morning dip (M) with the lowest reading in the morning and (P) or double dip with the lowest readings morning and evening. Regular patterns were most frequently seen in asthmatics, but occurred also in bronchitis, particularly those with a history of wheeze. Treatment with bronchodilators reduces the prevalence of all regular patterns but does not abolish them. M pattern is characteristic of asthma but P pattern is the most frequent regular pattern seen in bronchitis. Amplitude of variation is greater in asthmatics than in simple bronchitis. It is reduced by about 20% with bronchodilators. Random observation of magnitude of response of peak flow rate to a bronchodilators is not a good indicator of amplitude of variation over the day. Because of the occurrence of a peak pattern in many patients the magnitude of diurnal variation may be underestimated by twice-daily peak flow rate readings. Treatment with corticosteroids does not appear strongly to influence either characteristic patterns or amplitude of variation.     

Upper airway obstruction in hypothyroidism

Abstract. Objectives. To determine the occurrence and frequency of nocturnal upper airway obstruction in hypothyroidism. Design. A case-control study of patients with newly diagnosed hypothyreosis and euthyroid subjects who had been selected from the population register. The subjects underwent sleep recordings with a static-charge-sensitive bed (SCSB). Setting. Turku University Hospital and Research and Development Unit, Social Insurance Institution, Turku, Finland. Subjects. Twenty six consecutive patients underwent sleep recordings with SCSB and a pulse oximeter. One hundred and eighty-eight euthyroid subjects who were previously studied with the SCSB were used as controls. Main outcome measures. In a multivariate analysis, hypothyroidism, gender, age, and body mass index (BMI) were considered as predictors for the occurrence of nocturnal breathing abnormalities. Results. Nocturnal breathing abnormalities were frequent in both groups. Fifty per cent of the hypothyroid patients and 29.3% of the control subjects had at least some episodes of partial or complete upper airway obstruction (P = 0.04). Severe obstruction with episodes of repetitive apnoea was present in 7.7% of the patients and in 1.5% of the controls. The multivariate analysis revealed that the presence of hypothyroidism did not significantly (P = 0.06), and independently of age, BMI or gender, predict nocturnal breathing abnormalities, whereas obesity (P < 0.0001) and male gender (P = 0.0001) were independent and significant predictors. Conclusions. The incidence of nocturnal upper airway obstruction is increased in hypothyroidism, but is related to obesity and male gender rather than to hypothyroidism per se.     

Should forced expiratory volume in six seconds replace forced vital capacity to detect airway obstruction?

It has been suggested that forced expiratory volume in six seconds (FEV(6)) should be substituted for forced vital capacity (FVC) to measure fractions of timed expired volume for airflow obstruction detection. The present authors hypothesised that this recommendation might be questionable because flow after 6 s of forced expiration from more diseased lung units with the longest time constants was most meaningful and should not be ignored. Furthermore, previous studies comparing FEV(6) and FVC included few subjects with mild or no disease. The present study used spirometric data from the USA Third National Health and Nutrition Evaluation Survey with prior published ethnicity- and sex-specific equations for FEV(1)/FEV(6), FEV(1)/FVC and FEV(3)/FVC, and new equations for FEV(3)/FEV(6), all derived from approximately 4,000 adult never-smokers aged 20-80 yrs. At 95% confidence intervals, 21.3% of 3,515 smokers and 41.3% of smokers aged >51 yrs had airway obstruction; when comparing FEV(1)/FEV(6) with FEV(1)/FVC, 13.5% were concurrently abnormal, 1.5% were false positives and 4.1% were false negatives; and when comparing FEV(3)/FEV(6) with FEV(3)/FVC, 11.6% were concurrently abnormal, 3.3% were false positives and 5.7% were false negatives. Substituting forced expiratory volume in six seconds for forced vital capacity to determine the fractional rates of exhaled volumes reduces the sensitivity of spirometry to detect airflow obstruction, especially in older individuals and those with lesser obstruction.     

Bronchodilator response to ipratropium bromide in infants with bronchopulmonary dysplasia

Although the muscarinic antagonist Ipratropium bromide is used clinically as a bronchodilator in infants ventilated because of bronchopulmonary dysplasia (BPD), no studies have compared the response or efficacy of different dosages or its effectiveness in combination with beta-adrenergic agonists. We measured the response of respiratory system mechanics in 10 ventilated infants (25 +/- 2 days of age) to 75, 125, and 175 micrograms ipratropium bromide (IB), 125 micrograms IB plus 0.04 mg salbutamol (SAL), 175 micrograms IB plus 0.04 mg SAL, and saline vehicle, delivered via nebulizer into the ventilator circuit. Respiratory system resistance (Rrs) and compliance (Crs) were measured by the passive flow-volume technique. Rrs and Crs were measured before and at 1 to 2 h and at 4 h after delivery of the five drug dosages or saline. All six studies were completed within a 72-h period. Saline had no significant effect on mechanics. Significant responses to ipratropium alone were seen only after 175 micrograms where Rrs decreased 20 +/- 3% (SEM) (p less than 0.05) at 1 to 2 h and 16 +/- 5% (p less than 0.05) at 4 h. After 125 micrograms IB + SAL and 175 micrograms IB + SAL, Rrs was significantly decreased both at 1 to 2 h and at 4 h, and Crs was significantly increased 20 +/- 6% and 20 +/- 4%, respectively, at 1 to 2 h. The greatest decrease in Rrs (26 +/- 6%) was seen 1 to 2 h after 175 micrograms IB + salbutamol.(ABSTRACT TRUNCATED AT 250 WORDS)