Determinants of adherence in adults with cystic fibrosis.

Cystic fibrosis (CF) is now as much a disease of adults as of children and adolescents. An important focus of recent research has been the impact of the complex, expensive, and time consuming routine of self-care and medical treatment that is required by adults with CF to maintain health. A growing concern for medical and allied health teams is the issue of patient adherence to prescribed health management plans. A summary of the particular medical and treatment context of CF is followed by a review of adherence measurement issues and the determinants of adherence to treatment regimens in people with CF, primarily adults. Evidence for factors which influence adherence decisions of people with CF is examined. The medical and psychological aspects of this complex problem have not been adequately addressed because of difficulties with definition and measurement. Only a small proportion of the variance in adherence has been accounted for in the literature. New measurement technologies and new theoretical directions offer promise for a better understanding of this complex and important issue and may result in more effective intervention strategies to improve adherence.

Arterial hypoxaemia in endurance athletes is greater during running than cycling.

The effect of both training discipline and exercise modality on exercise-induced hypoxaemia (EIH) was examined in seven runners and six cyclists during 5 min high intensity treadmill and cycle exercise. There were no significant interactions between training discipline, exercise modality and arterial P(O(2)) (Pa(O(2))) when subject groups were considered separately but when pooled there were significant differences between exercise modalities. After min 2 of exercise arterial hydrogen ion concentration, minute ventilation, alveolar P(O(2)) (PA(O(2))) and Pa(O(2)) were all lower with treadmill running with the largest differential for the latter occurring at min 5 (treadmill, 80.8+/-1.8; cycle, 90.2+/-2.5, mmHg, N=13, P< or = 0.05). At every min of exercise, the differences in Pa(O(2)) between the ergometers were strongly associated with similar differences in PA(O(2)) and alveolar to arterial P(O(2)) (PA(O(2))-Pa(O(2))). It is concluded that the greater EIH with treadmill running is a consequence of the combined effect of a reduced lactic acidosis-induced hyperventilation and greater ventilation-perfusion inequality with this exercise mode.

Pulmonary gas exchange during exercise in highly trained cyclists with arterial hypoxemia.

The causes of exercise-induced hypoxemia (EIH) remain unclear. We studied the mechanisms of EIH in highly trained cyclists. Five subjects had no significant change from resting arterial PO(2) (Pa(O(2)); 92.1 +/- 2.6 Torr) during maximal exercise (C), and seven subjects (E) had a >10-Torr reduction in Pa(O(2)) (81.7 +/- 4.5 Torr). Later, they were studied at rest and during various exercise intensities by using the multiple inert gas elimination technique in normoxia and hypoxia (13.2% O(2)). During normoxia at 90% peak O(2) consumption, Pa(O(2)) was lower in E compared with C (87 +/- 4 vs. 97 +/- 6 Torr, P < 0.001) and alveolar-to-arterial O(2) tension difference (A-aDO(2)) was greater (33 +/- 4 vs. 23 +/- 1 Torr, P < 0. 001). Diffusion limitation accounted for 23 (E) and 13 Torr (C) of the A-aDO(2) (P < 0.01). There were no significant differences between groups in arterial PCO(2) (Pa(CO(2))) or ventilation-perfusion (VA/Q) inequality as measured by the log SD of the perfusion distribution (logSD(Q)). Stepwise multiple linear regression revealed that lung O(2) diffusing capacity (DL(O(2))), logSD(Q), and Pa(CO(2)) each accounted for approximately 30% of the variance in Pa(O(2)) (r = 0.95, P < 0.001). These data suggest that EIH has a multifactorial etiology related to DL(O(2)), VA/Q inequality, and ventilation.

Exercise-induced hypoxaemia in highly trained cyclists at 40% peak oxygen uptake.

A group of 15 competitive male cyclists [mean peak oxygen uptake, VO2peak 68.5 (SEM 1.5 ml x kg(-1) x min(-1))] exercised on a cycle ergometer in a protocol which began at an intensity of 150 W and was increased by 25 W every 2 min until the subject was exhausted. Blood samples were taken from the radial artery at the end of each exercise intensity to determine the partial pressures of blood gases and oxyhaemoglobin saturation (SaO2), with all values corrected for rectal temperature. The SaO2 was also monitored continuously by ear oximetry. A significant decrease in the partial pressure of oxygen in arterial blood (PaO2) was seen at the first exercise intensity (150 W, about 40% VO2peak). A further significant decrease in PaO2 occurred at 200 W, whereafter it remained stable but still significantly below the values at rest, with the lowest value being measured at 350 W [87.0 (SEM 1.9) mmHg]. The partial pressure of carbon dioxide in arterial blood (PaCO2) was unchanged up to an exercise intensity of 250 W whereafter it exhibited a significant downward trend to reach its lowest value at an exercise intensity of 375 W [34.5 (SEM 0.5) mmHg]. During both the first (150 W) and final exercise intensities (VO2peak) PaO2 was correlated significantly with both partial pressure of oxygen in alveolar gas (P(A)O2, r = 0.81 and r = 0.70, respectively) and alveolar-arterial difference in oxygen partial pressure (P(A-a)O2, r = 0.63 and r = 0.86, respectively) but not with PaCO2. At VO2peak PaO2 was significantly correlated with the ventilatory equivalents for both oxygen uptake and carbon dioxide output (r = 0.58 and r = 0.53, respectively). When both P(A)O2 and P(A-a)O2 were combined in a multiple linear regression model, at least 95% of the variance in PaO2 could be explained at both 150 W and VO2peak. A significant downward trend in SaO2 was seen with increasing exercise intensity with the lowest value at 375 W [94.6 (SEM 0.3)%]. Oximetry estimates of SaO2 were significantly higher than blood measurements at all times throughout exercise and no significant decrease from rest was seen until 350 W. The significant correlations between PaO2 and P(A)O2 with the first exercise intensity and at VO2peak led to the conclusion that inadequate hyperventilation is a major contributor to exercise-induced hypoxaemia.

Pulmonary disease from exposure to an artificial aluminium silicate: further observations.

A cross sectional analysis of the relation between exposure to an artificial aluminium silicate (alunite residue) and pulmonary function changes has been made in 32 subjects, 17 of whom had been previously reported and in whom there was suggestive evidence of a dose response relation between gas transfer and total silicate exposure. Longitudinal data were also available for nine subjects. No dose effect relation was observed in either analysis and only one of the three subjects previously observed to have an abnormal chest radiograph (the index subject) had deteriorated appreciably. Respirable particles of alunite residue were injected intratracheally into Syrian hamsters. No evidence of pulmonary toxicity was seen as judged by bronchoalveolar lavage measurements of the concentrations lactic dehydrogenase, albumin, and the lambda fraction of gold, and the numbers of macrophages, polymorphonuclear cells, and red blood cells (alpha-quartz and ferrous oxide were used as positive and negative controls). These results do not support a significant toxic effect of this aluminium silicate on the lungs.

Density dependence of maximal flow is lung volume dependent during bronchoconstriction.

We examined the changes in maximum expiratory flow (Vmax) and the density dependence of maximum expiratory flow (delta Vmax) during histamine-induced bronchoconstriction in dogs. Histamine acid phosphate solution was nebulized into the airways of six dogs to produce predominantly peripheral airway obstruction. Vmax air, Vmax with the dogs breathing 80% He-20% O2 (delta Vmax), and airway sites of flow limitation (choke points) were examined at four lung volumes (VL), which ranged from 51 to 23% of the control vital capacity (VC). The findings were interpreted in terms of the wave-speed theory of flow limitation. At all VL, Vmax air decreased during bronchoconstriction by approximately 30% compared with the control value. Resistances peripheral to a 0.3-cm-diam airway were increased about threefold with histamine, whereas resistances between 0.6-cm-diam bronchi and main-stem bronchi increased just slightly. Airway diameters were measured in the air-dried lung at 20 cmH2O transpulmonary pressure. Our results showed that only at 44% VC did delta Vmax decrease in all experiments after histamine to indicate peripheral obstruction (mean: 68.5 to 45%). At 23% VC, delta Vmax increased slightly, from 22 to 28%. At 23 and 36% VC, substantial differences in the wave-speed variables between air and HeO2 were present before bronchoconstriction, so that delta Vmax was low in some dogs, although peripheral airway obstruction was not evident. When bronchoconstriction was produced, delta Vmax at 23% VC could not be decreased further and even increased in four of six dogs. Thus changes in delta Vmax at given lung volume may not reflect the predominant site of airflow obstruction during bronchoconstriction.

Mechanism of reduced maximum expiratory flow in dogs with compensatory lung growth.

We examined the mechanism of the reduced maximum expiratory flow rates (Vmax) in a dog model of postpneumonectomy compensatory lung growth. During forced expiration, a Pitot-static tube was used to locate the airway site of flow limitation, or choke point, and to measure dynamic intrabronchial pressures. The factors determining Vmax were calculated and the results analyzed in terms of the wave-speed theory of flow limitation. Measurements were made at multiple lung volumes and during ventilation both with air and with HeO2. Five of the puppies had undergone a left pneumonectomy at 10 wk of age, and 5 littermate controls had undergone a sham operation. All dogs were studied at 26 wk of age, at which time compensatory lung growth had occurred in the postpneumonectomy group. Vmax was markedly decreased in the postpneumonectomy group compared with control, averaging 42% of the control flow rates from 58 to 35% of the vital capacity (VC). At 23% of the VC, Vmax was 15% less than control. Choke points were more peripheral in the postpneumonectomy dogs compared with controls at all volumes. The total airway pressure was the same at the choke-point airway in the postpneumonectomy dogs as that in the same airway in the control dogs, suggesting that the airways of the postpneumonectomy dogs displayed different bronchial area-pressure behavior from the control dogs. Despite the decreased Vmax on both air and HeO2, the density dependence of flow was high in the postpneumonectomy dogs and the same as controls at all lung volumes examined.

Irreversible airflow obstruction. Evolution in asthma.

To determine whether asthma can cause irreversible airflow obstruction (IAO) 89 subjects with uncomplicated asthma received intensive treatment for four weeks. FEV1 was measured at 0, two and four weeks; pulmonary elasticity and flow resistance was measured in 46 of the subjects at four weeks. Severity of asthma and cigarette consumption were ascertained by a questionnaire. The mean difference between the predicted and highest FEV1 during treatment was 0.29 L (P less than 0.001). The highest FEV1% predicted correlated (P less than 0.001) with the duration and severity of asthma in the entire group, in the 51 nonsmokers, and in the 47 subjects with the adult onset of asthma. Pulmonary resistance, but not elastic recoil, correlated with the duration and severity of asthma (P less than 0.01). The results show that chronic asthma can cause narrowed airways and IAO, and suggest that this may be prevented by improved control of asthma.

Dynamic lung function in dogs with compensatory lung growth.

Nine puppies underwent left pneumonectomy at 10 wk of age while nine sex-matched littermates had a sham operation, and all animals were studied at 25 wk of age. Postpneumonectomy dogs demonstrated compensatory growth in that lung weight and total lung capacity (TLC) were the same as those of control animals when normalized for body weight. In postpneumonectomy dogs all lobes of the remaining right lung increased in weight, but this was most notable in the cardiac lobe which grew across the mediastinum. Subdivisions of lung volume were normal in postpneumonectomy animals except for residual volume (RV): RV/TLC was increased when compared with control animals. In intact dogs static pressure-volume curves of the lung and respiratory system did not differ between groups, and the static pressure-volume curves of excised lungs were closely similar. Maximum expiratory flow was sharply reduced in postpneumonectomy dogs, averaging 40% of flow in control dogs over the lower 50% of the vital capacity. In both groups the fractional increase in maximal expiratory flow during HeO2 breathing was substantial and similar. Regional compliances, resistances, and perfusion distribution were examined using 133Xe. Regional compliance and perfusion were reduced in the left hemithorax of postpneumonectomy dogs while regional resistances were increased.

Asthma and irreversible airflow obstruction.

To determine whether asthma alone can cause irreversible airflow obstruction 42 men and 47 women with chronic asthma (mean duration 22 (SD 13) years) without evidence of other disease likely to cause irreversible airflow obstruction were treated with theophylline orally and a beta agonist both orally and by inhalation for four weeks. After two weeks of treatment the FEV1 was less than 85% of the predicted normal value (%P) in 48 patients and these individuals then received prednisolone 0.6 mg/kg/day for two weeks. Duration and severity of asthma and smoking history were quantified by questionnaire; 38 patients were current smokers or ex-smokers. FEV1 was measured at 0, 2, and 4 weeks. The mean difference between the best FEV1 during the study and the predicted normal value was 0.29 l (p less than 0.001); FEV1 %P decreased with age (r = -0.30, p less than 0.01) and with the duration (r = -0.47, p less than 0.001) and severity (r = -0.55, p less than 0.001) of asthma. Similar findings were noted when the results for non-smokers and those whose asthma started in adult life were analysed separately. We conclude that asthma alone can cause irreversible airflow obstruction and that the degree of obstruction is a function of the duration and severity of previous asthma. The results suggest the possibility that irreversible airflow obstruction in asthma may be preventable by minimising the degree of persistent asthma.

Effect of previous volume history on airway closure.

We studied the effect of volume history on airway closure in six healthy males ranging from 32 to 67 yr of age. The method used was to compare the regional distribution of 133Xe boluses distributed according to N2O uptake during open-glottis breath-hold maneuvers with the regional distribution of boluses of intravenously injected 133Xe. Measurements were made at two lung volumes, one close to residual volume (RV) and the other just below closing volume. The required volume was reached either by expiring from total lung capacity or by inspiring from RV. Although there was considerable airway closure in the basal regions of the lungs at both lung volumes studied, the degree of airway closure was not dependent on the previous volume history. We conclude that the airways concerned with closure have a volume-pressure hysteresis similar to that of the lung parenchyma. Furthermore in normal humans the volume-pressure hysteresis of the lung is not secondary to airway closure.

Pulmonary disease from occupational exposure to an artificial aluminium silicate used for cat litter.

All available workers engaged in bagging an artificial crystalline aluminium silicate--the kiln-dried residue from the calcining and water extraction of alunite (a hydrated sulphate of aluminium and potassium) that is currently classified as a nuisance dust--were studied after a complaint of respiratory and systemic symptoms, including arthritis, by an employee of the factory, who showed physiological and radiographic evidence of diffuse pulmonary fibrosis and in whom lung biopsy showed diffuse fibrosis with granulomas. Inhalation challenge produced a transient decrease in transfer factor and transfer factor standardised for alveolar volume. Twenty-five subjects were known to have been exposed at some time to the dust of alunite-residue. Of the 17 who could be contacted, all agreed to attend for respiratory questionnaire and occupational history, pulmonary function testing (spirometry, lung volumes, gas transfer), and posteroanterior chest radiograph. Six subjects considered that occupational exposure to the dust was responsible for respiratory symptoms. Three subjects had abnormality of the chest radiograph consistent with pulmonary fibrosis. The mean percentage of predicted transfer factor standardised for effective alveolar volume was 71.1% in subjects with abnormal chest radiographs and 86.6% in subjects with normal radiographs (p = 0.10). There was a trend in the correlation between the percentage of predicted transfer factor standardised for effective alveolar volume and total dust exposure (sum of the products of grade of severity of each exposure period and duration of each exposure period in months) (r = 0.40 p = 0.10). This study suggests that there may be a relation between inhalation of the dust of this form of aluminium silicate and pulmonary fibrosis.