Predicting worsening asthma control following the common cold.

The asthmatic response to the common cold is highly variable, and early characteristics that predict worsening of asthma control following a cold have not been identified. In this prospective multicentric cohort study of 413 adult subjects with asthma, the mini-Asthma Control Questionnaire (mini-ACQ) was used to quantify changes in asthma control and the Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21) to measure cold severity. Univariate and multivariable models were used to examine demographic, physiological, serological and cold-related characteristics for their relationship to changes in asthma control following a cold. Clinically significant worsening of asthma control was observed following a cold (mean+/-SD increase in mini-ACQ score of 0.69+/-0.93). Univariate analysis demonstrated that season, centre location, cold duration and cold severity measurements were all associated with a change in asthma control. Multivariable analysis of the covariates available within the first 2 days of cold onset revealed that the day 2 and cumulative sum of day 1 and 2 WURSS-21 scores were significant predictors of the subsequent changes in asthma control. In asthmatic subjects, cold severity within the first 2 days can be used to predict subsequent changes in asthma control. This information may help clinicians prevent deterioration in asthma control following a cold.

Acute interstitial pneumonitis. Case series and review of the literature.

Acute interstitial pneumonitis (AIP) is an acute, idiopathic interstitial lung disease characterized by rapidly progressive diffuse pulmonary infiltrates and hypoxemia requiring hospitalization. The case-fatality ratio is high. Previous reports suggested that survivors of the acute event have a favorable outcome. We undertook this study to examine the natural history of survivors. We had observed several patients who experienced recurrent episodes of AIP and chronic progressive interstitial lung disease. We sought to determine longitudinal survival in these patients and to compare our experience with that in the medical literature. Overall, we identified 13 biopsy-proven cases of AIP. The mean patient age was 54 years in our review, which is identical to previous reports. Twelve patients were hospitalized and all 12 required mechanical ventilation. Overall hospital survival was 67%. All patients demonstrated abnormalities in gas exchange at presentation. Radiographs typically demonstrated bilateral patchy densities that progressed to a diffuse alveolar filling pattern in nearly all cases. All biopsy specimens showed organizing diffuse alveolar damage. Longitudinal data were available for 7 patients. Two died of AIP recurrences. A third died of complications of heart failure shortly after hospital discharge. One patient progressed to end-stage lung disease and required lung transplantation. Two patients experienced persistent pulmonary symptoms, accompanied in 1 by progressive lung fibrosis. One patient had nearly complete recovery of lung function 2 years following AIP. (Follow-up information was unavailable for 2 survivors.) In our literature review, 5 of 7 patients reported experienced some recovery of lung function. One case of progressive interstitial lung disease requiring lung transplantation was reported. The reported mortality was much higher than in our experience (74% versus 33%). The mean time from symptom onset to death was 26 days, compared with 34 days in our experience. The use of corticosteroids did not appear to influence survival, although this has not been tested in a rigorous manner. The better survival in our series may be related in part to a survivor selection bias. In contrast to previous reports, we found that survivors of AIP may experience recurrences and chronic, progressive interstitial lung disease. We did not identify any clinical or pathologic features that predict mortality in these patients. Likewise, there were no features that predicted the longitudinal course in survivors. Further study to identify causal factors is required in the hope of preventing morbidity and mortality related to this disease.

Gas exchange at a given degree of volume restriction is different in sarcoidosis and idiopathic pulmonary fibrosis.

PURPOSE: It is likely that the relationship between lung volume changes and gas exchange in patients with idiopathic pulmonary fibrosis (IPF) and patients with sarcoidosis is different since the two conditions vary widely in histopathology and prognosis. Few studies, however, have examined this relationship. The goal of this investigation was to measure diffusing capacity and gas exchange in patients with IPF and sarcoidosis in whom the reduction of lung volume was equivalent. PATIENTS AND METHODS: In 21 patients with IPF and 20 patients with pulmonary sarcoidosis with comparable reductions in lung volume, the single breath diffusing capacity for carbon monoxide and gas exchange at rest and during exercise were compared. RESULTS: The relationship between lung volume and gas transfer differed in the two groups of patients. Resting and exercise gas exchange tended to be relatively normal and the diffusing capacity was higher in patients with sarcoidosis than in those with IPF. These differences could not be attributed to disparities in race, age, smoking habits, or the radiographic stage of sarcoidosis. CONCLUSION: The preservation of gas exchange in sarcoidosis as opposed to IPF, despite equivalent degrees of volume restriction, suggests that different pathophysiologic mechanism underlie the volume loss and gas exchange defects seen in these disorders. Furthermore, these findings suggest that diffusing capacity may not be a sensitive indicator of pulmonary pathology in sarcoidosis since lung volume can be altered independently of abnormalities in the diffusing capacity.

The utility of spirometry in the diagnosis of reversible airways obstruction.

Patients with suspected reversible airways obstruction (RAO) sometimes report subjective benefit after bronchodilator treatment despite no objective spirometric improvement. One possible explanation for this is improvement in volume-related or plethysmographic parameters in the absence of spirometric improvement. One hundred patients with RAO were assessed before and after inhaled bronchodilator to determine the prevalence of improvement by plethysmographic parameters in the absence of improvement in spirometric parameters. Spirometry alone (FEV1, FVC, and FEF25-75%) identified reversibility of airflow limitation in 82 patients. Reversibility was identified by body plethysmography (specific conductance [SGaw], thoracic gas volume [TGV], and isovolume maximum expiratory flow rates [IVMEF]) in 15 of the remaining patients. The percent predicted FEF25-75% at baseline was higher in patients who required plethysmography to identify reversibility, but could not be used to predict the lack of a spirometric response for any individual patient. We conclude that spirometry alone fails to identify reversibility in approximately 15 percent of patients, and that most of these patients can be identified by additional plethysmographic measurements of volume-related parameters. At any one point in time, multiple tests must be used together to adequately identify the majority of patients with reversible airways obstruction. Improvement in volume-related parameters may explain why some patients with RAO improve subjectively with bronchodilators but show no spirometric improvement.

Attenuation of the metabisulfite-induced bronchoconstrictive response by pretreatment with cromolyn.

In a retrospective analysis of 1,544 patients who underwent provocative challenge with metabisulfite at the National Jewish Center between 1983 and 1987, an abnormal airway response to metabisulfite was found in 52 patients, an incidence of 3.4 percent. There was no relationship between this abnormal airway responsiveness to metabisulfite and the degree of airway obstruction present, or the degree of airway reactivity as assessed by the response to inhaled bronchodilator or exercise testing. In a pilot study, we found that the administration of cromolyn sodium prior to metabisulfite challenge markedly attenuated the abnormal bronchoconstrictive response in nine of ten patients. We conclude that a metabisulfite-induced bronchoconstrictive response cannot be predicted on the basis of the degree of airway obstruction or airway reactivity and that pretreatment with cromolyn sodium may attenuate the abnormal response.

Efficacy of a pulsed oxygen delivery device during exercise in patients with chronic respiratory disease.

The ability of a pulsed oxygen delivery system (Puritan-Bennett Companion Oxygen Saver (COS-5) to track respiratory rate during exercise and the oxygenation achieved during the exercise while oxygen was being delivered by this system was compared to that attained while oxygen was delivered continuously in six patients with chronic obstructive pulmonary disease (COPD) and six patients with idiopathic pulmonary fibrosis (IPF). The COS-5 appeared to respond appropriately at respiratory rates between 15 and 45, even when there were minimal pressure changes at the nose. There was an excellent correlation in PaO2 at equivalent flow settings during the exercise in the patients with COPD and IPF. There were six instances (in four patients) of the 31 comparisons in which the PaO2 differed by more than 5 mm Hg. The PaO2 was higher with continuous oxygen delivery on two occasions in a patient with COPD who utilized pursed-lip breathing during the exercise. The PaO2 was higher with COS-5 delivery on two occasions in a patient with IPF who was breathing at the highest respiratory rates (44 and 45/min) during the exercise.

Methacholine challenge testing: safety of low starting FEV1. Asthma Clinical Research Network (ACRN).

STUDY OBJECTIVE: The lower limit for the baseline value to initiate methacholine bronchial hyperresponsiveness testing has not been well established. Recommendations have varied from > 1 L to above 80% of predicted. The objective was to determine if an FEV1 < 60% predicted was acceptable. DESIGN: Retrospective analysis of challenges in 88 patients with a baseline FEV1 of < 60% predicted (mean=45.8%; range, 22 to 59%. SETTING: Academic institutions. RESULTS: There were only four individuals whose FEV1 did not return to > 90% of baseline following one poststudy beta2-agonist treatment. All four responded to a second treatment. There were no adverse sequelae following challenge in any individual. Neither age (up to 79 years) nor gender influenced outcome. CONCLUSIONS: In chronic moderate to severe asthma, it appears that bronchial hyperresponsiveness testing can be safely performed even in those patients with a low baseline FEV1.

The utility of peak flow, symptom scores, and beta-agonist use as outcome measures in asthma clinical research.

STUDY OBJECTIVES: Several methods of utilizing peak expiratory flow (PEF) and other markers of disease activity have been suggested as useful in the management of asthma. It remains unclear, however, as to which surrogate markers of disease status are discriminative indicators of treatment failure, suitable for use in clinical trials. DESIGN: We analyzed the operating characteristics of 66 surrogate markers of treatment failure using a receiver operating characteristic (ROC) curve analysis. PARTICIPANTS: Information regarding FEV(1), symptoms, beta(2)-agonist use, and PEF was available from 313 subjects previously enrolled in two Asthma Clinical Research Network trials, in which 71 treatment failures occurred (defined by a 20% fall in FEV(1) from baseline). INTERVENTIONS: None. MEASUREMENTS AND RESULTS: None of the measures had an acceptable ability to discriminate subjects with a > or % fall in FEV(1) from those without, regardless of the duration of the period of analysis or the criteria for test positivity employed. Areas under the ROC curves generated ranged from 0.51 to 0.79, but none were statistically superior. Sensitivity and specificity combinations were generally poor at all cutoff values; true-positive rates could not be raised without unacceptably elevating false-positive rates concurrently. CONCLUSIONS: Studies that seek to detect treatment failure defined by a significant fall in FEV(1) should not use such individual surrogate measures to estimate disease severity.

Physiologic diagnosis and function in asthma.

Asthma is a condition in which there is airway hyperresponsiveness, with the propensity for widespread, reversible airways narrowing on exposure to diverse inciting factors (triggers). Inhalation of nonspecific agents such as methacholine or histamine leads to bronchoconstriction in most cases, and in some, the bronchoconstriction follows exposure to specific agents such as antigen or occupational irritants. Chest tightness and cough, which are the most common symptoms of asthma, are probably the result of inflammation mucus plugs, edema, or smooth muscle constriction in the small peripheral airways. Because major obstruction of the peripheral airways can occur without recognizable increases of airway resistance or FEV1, the physiologic alterations in acute exacerbations are generally subtle in the early stages. Poorly ventilated alveoli subtending obstructed bronchioles continue to be perfused, and as a consequence, the P(A-a)O2 increases and the PaO2 decreases. At this stage, ventilation is generally increased, with excessive elimination of carbon dioxide and respiratory alkalemia. In the more severe exacerbation, lung volume is increased and the static volume-pressure curve is shifted up (lung volume is greater) and to the left (pressure is lower) while the shape of the curve is unaltered. The airway obstruction is reversible and there is generally improvement in air flow rates following administration of beta-agonists and anti-inflammatory agents. The changes in mechanical properties are also reversible, and therapeutic intervention usually results in a shift of the PV curve downward toward the normal position, for example, a decrease in TLC and an increase in the elastic recoil pressure at any particular lung volume. Failure to take these changes into account may underestimate the impact of therapy. The PaO2 decreases (and the P(A-a)O2 increases) as the work of breathing increases, and when it becomes excessive (and/or the FEV1 falls below 20% to 25%), the PaCO2 begins to increase. Therefore, in any patient with asthma, a decreasing PaO2 and an increasing PaCO2, even into the normal range, indicates severe airway obstruction that is leading to respiratory muscle fatigue and patient exhaustion.

Bleomycin-induced lung disease in an animal model: correlation between computed tomography-determined abnormalities and lung function.

RATIONALE AND OBJECTIVES: The authors evaluated whether specific types of computed tomographic (CT) abnormalities could be correlated with physiologic impairment in animals with bleomycin-induced lung injury. METHODS: Lung injury was induced in 20 rabbits by means of intratracheal administration of bleomycin (3 U per kilogram of body weight), followed by 100% oxygen for 2 minutes. The animals underwent high-resolution CT scanning at 14 (n = 4), 28 (n = 6), or 56 (n = 10) days after injury. CT morphometry was used to determine the extent of abnormal lung. Physiologic evaluation was performed before injury and before scanning. RESULTS: The overall extent of abnormal lung and of parenchymal opacification on CT scans did not correlate with any physiologic variable. The extent of interstitial thickening correlated significantly with total lung capacity (r = -.783, P = .0005), airway pressure at maximal lung volume (r = .836, P = .0001), and alveolar-arterial oxygen gradient (r = .613, P = .004). CONCLUSION: CT findings of interstitial thickening are associated with impaired gas exchange and lung stiffness in rabbits.

Laryngeal dysfunction and pulmonary disorder.

The normal respiratory function of the larynx has been described in detailed reports in both the otolaryngology and the respiratory physiology literature. The role of the posterior cricoarytenoid muscle in vocal cord abduction has been shown to be paramount in laryngeal respiratory function. However, only in recent reports has attention been directed toward disordered laryngeal function as evidenced in pulmonary disorders, such as asthma, or in association with underlying pulmonary disorders, such as asthma (ROAD) or emphysema (COPD). In this article, cases will be presented to demonstrate the role of disordered laryngeal function appearing as pulmonary disease and associated with various degrees of underlying pulmonary disease. The effect on pulmonary function tests and the role of treatment will be discussed.

Evaluation of respiratory function in health and disease.

From a conceptual standpoint, the tests of pulmonary function can be divided into those that assess the ventilatory function of the lungs and those concerned with gas exchange. Tests of ventilatory function reflect alterations of the elastic resistance and flow resistance of the respiratory apparatus. The elastic properties of the lungs are assessed by determining the position and shape of the curve representing the relationship between the pressure across the lungs and absolute lung volume. When there is reduced distensibility of either the lungs or the chest wall, the volume-pressure curve is shifted down and to the right. The slope of the curve is reduced in the patient with pulmonary fibrosis, while it is normal in the patient with obesity. In asthma (or chronic bronchitis) and emphysema, the volume-pressure curve is shifted up and to the left. In emphysema, the slope of the curve is increased, while it is normal in patients with asthma or bronchitis. In practice, lung volume is used as an index of alterations of the volume-pressure characteristics of the lungs and/or chest wall. The vital capacity is often used as a surrogate for the TLC but it is lower than expected in both restrictive and obstructive disorders. The FEV1.0 reflects the degree of expiratory flow limitation. In a restrictive disorder, lung volume and the FEV1.0 are reduced, but the FEV1.0/FVC ratio is normal. In airflow limitation, lung volume, the FEV1.0, and the FEV1.0/FVC ratio are lower than expected. In airflow limitation, the reversibility with inhaled bronchodilator should be determined. Tests of airway responsiveness are indicated when evaluating patients with unexplained chronic cough, chest tightness, or wheezing, particularly if other lung function tests are normal. The adequacy of gas exchange is assessed by determining the arterial blood gas tensions--PaO2 and PaCO2--and the alveoloarterial pO2 gradient--P(A-a)O2. A lower-than-expected PaO2 can result from several different physiologic disturbances. When alveolar hypoventilation is the sole disturbance, the oxygen in the alveoli and in the blood perfusing them virtually comes into equilibrium, so that the P(A-a)O2 is normal. An elevated P(A-a)O2 is caused by either mismatching of ventilation and perfusion, true venous admixture, a diffusion abnormality, or a combination of these disturbances. Because dyspnea on exertion is a cardinal symptom of respiratory disease, exercise tolerance should be assessed. A reduced exercise tolerance may result from ventilatory limitation, impaired gas exchange, cardiac impairment, impaired delivery of the oxygen to the working muscles, or an inability to use the energy.

Chronic and acute asthma. Keys to successful management.

The goal of chronic asthma management is to maintain maximal bronchodilation, which is achieved by regular monitoring of ventilatory function and by use of bronchodilators. A trial of corticosteroid is justified if symptoms are not controlled and marked improvement in forced expiratory volume in one second is not achieved by appropriate use of bronchodilating agents. Corticosteroids should also be used if symptoms exacerbate. If hospitalization is required, a more rigorous therapeutic program, which may involve oxygenation, aminophylline and/or corticosteroid administration, fluid therapy, and ventilatory support, should be instituted.