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Biomedical subjects

James F Donohue

Publications and source records attributed to James F Donohue.

At least 19 recordsLinked to original sources
PubMed2006

Infliximab therapy in patients with chronic sarcoidosis and pulmonary involvement.

RATIONALE: Evidence suggests that tumor necrosis factor (TNF)-alpha plays an important role in the pathophysiology of sarcoidosis. OBJECTIVES: To assess the efficacy of infliximab in sarcoidosis. METHODS: A phase 2, multicenter, randomized, double-blind, placebo-controlled study was conducted in 138 patients with chronic pulmonary sarcoidosis. Patients were randomized to receive intravenous infusions of infliximab (3 or 5 mg/kg) or placebo at Weeks 0, 2, 6, 12, 18, and 24 and were followed through Week 52. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was the change from baseline to Week 24 in percent of predicted FVC. Major secondary efficacy parameters included Saint George's Respiratory Questionnaire, 6-min walk distance, Borg's CR10 dyspnea score, and the proportion of Lupus Pernio Physician's Global Assessment responders for patients with facial skin involvement. Patients in the combined infliximab groups (3 and 5 mg/kg) had a mean increase of 2.5% from baseline to Week 24 in the percent of predicted FVC, compared with no change in placebo-treated patients (p = 0.038). No significant differences between the treatment groups were observed for any of the major secondary endpoints at Week 24. Results of post hoc exploratory analyses suggested that patients with more severe disease tended to benefit more from infliximab treatment. CONCLUSIONS: Infliximab therapy resulted in a statistically significant improvement in % predicted FVC at Week 24. The clinical importance of this finding is not clear. The results of this Phase 2 clinical study support further evaluation of anti-TNF-alpha therapy in severe, chronic, symptomatic sarcoidosis.

Adult↗
PubMed2006

Multi-center study: the biochemical efficacy, safety and tolerability of a new alpha1-proteinase inhibitor, Zemaira.

Augmentation therapy with a plasma derived alpha l-Proteinase Inhibitor (alpha1 -PI) has been demonstrated to be effective in restoring serum Alpha1 -antitrypsin (AAT)* levels in individuals with AAT Deficiency (note: alpha1 PI and AAT are synonymous). The objective of this study was to demonstrate that the steady-state trough serum alphal-PI levels, achieved by a new plasma derived alpha,-PI (Zemaira, study drug, ZLB Behring LLC, King of Prussia, Pennsylvania, USA), were bioequivalent to those achieved by the currently available alpha-PI therapy, Prolastin (control drug, Bayer Corporation, Berkeley, California, USA), and maintained weekly trough serum antigenic alpha1-PI levels above the protective threshold of 11 microM. This multi-center, controlled study randomized a total of 44 subjects to receive either study or control drug for a 10-week double-blind phase. The control group was then crossed over to receive the study drug for the remainder of the study (14 weeks). The difference in mean trough serum antigenic alpha1-PI level between the treatment groups was 1.45 microM (90% CI-2.77, -0.13), signifying bioequivalence. The mean trough serum antigenic alpha1-PI level in the study drug group was greater than the therapeutic threshold of 11 microM, achieving a level of 17.7 microM during the steady-state period. Treatment-related adverse events (AEs) were seen in 7% and 21% of study and control drug treated subjects, respectively. No documented viral transmission occurred. These results demonstrate that the new plasma derived alpha1-PI (Zemaira) is bioequivalent to the currently available product Prolastin, is well tolerated, and safe with respect to the risk of viral transmission.

Adolescent↗
PubMed2006

Comparison of sarcoidosis phenotypes among affected African-American siblings.

STUDY OBJECTIVE: To test the hypothesis that sibling pairs, who share genes and environmental exposures, might have similar phenotypic expressions of sarcoidosis beyond what would be expected by chance alone. DESIGN: Multicenter family study with study subjects recruited from 11 clinical centers. SUBJECTS: Subjects were African-American sibling pairs with sarcoidosis. Sarcoidosis and organ pattern involvement were defined according to specific criteria. Fifteen different organ systems were evaluated. RESULTS: For full-sibling pairs, ocular involvement was found in both siblings more often than expected by chance alone (p < 0.05), but the concordance was weak (kappa = 0.18). When analyzing full-sibling and half-sibling pairs, ocular and liver involvement showed a significant concordance between sibling pairs (p < 0.05), but again the agreement was poor (kappa = 0.16 for both). Concordance in pulmonary function change over time was also weak. Clinical outcomes of sibling pairs were not significantly correlated except for whether treatment was prescribed, and this level of agreement was poor (kappa = 0.14 for full-sibling and half-sibling pairs; kappa = 0.15 for full-sibling pairs only). Modeling phenotypic expression in sibling pairs using logistic regression did show that the presence of ocular and liver sarcoidosis in the first affected sibling conferred a statistically significant increased risk to the second affected sibling for having those organs involved (odds ratio [OR], 3; 95% confidence interval [CI], 1.7 to 5.4 for ocular; OR, 3.3; 95% CI, 1.5 to 7.4 for liver). CONCLUSIONS: The phenotypic features and clinical outcomes of sarcoidosis in sibling pairs show minimal concordance, with the possible exception that the presence of ocular or liver involvement in the first sibling with a diagnosis of sarcoidosis makes involvement of these organs more likely in other affected siblings.

Adult↗
PubMed2006

Long-acting beta-agonists role in asthma management.

The LABAs have played an important role in the management of asthma over the past decade. They are of clear benefit in reducing asthma-related symptoms and improving lung function when used in combination with an anti-inflammatory agent. Studies have shown, however, that their use has been associated with various negative outcomes, which has led to a restricted indication for salmeterol xinafoate (Serevent Diskus) and fluticasone propionate and salmeterol xinafoate (Advair Diskus), along with medication guides that will be given to patients with every new and refill prescription. Convincing data now exist that show an association of salmeterol with an increase in asthma-related deaths and life-threatening experiences, while formoterol is associated with more frequent serious asthma exacerbations. Nonetheless, LABAs remain an important component of asthma therapy. Further clarification about their role may occur with the release of additional analyses from SMART, as well as updated guidelines from the NAEPP Expert Panel, both expected later in 2006. In the meantime, LABAs and LABA-containing products are to be used only for patients not adequately controlled on other asthma-controller medications (eg, low- to medium-dose inhaled corticosteroids) or whose disease severity clearly warrants initiation of treatment with 2 maintenance therapies. The NHLBI/NAEPP guidelines recommend inhaled corticosteroids as the first step in controller therapy, with LABAs as an option if low- to medium-dose inhaled corticosteroids do not adequately control the patient's asthma".

Administration, Inhalation↗
PubMed2005

Effect of salmeterol on mucociliary and cough clearance in chronic bronchitis.

The effect of long acting beta(2)-adrenergic bronchodilators on impaired mucociliary clearance in chronic bronchitis is unknown. Using a radiolabeled aerosol (technetium-99m-labeled sulfur colloid) and gamma camera analysis, we measured the acute effect of salmeterol vs. placebo on mucociliary and cough clearance in mild-moderate chronic bronchitics (n = 14) over a 2h period. During the 1-1(1/2) h period of observation patients performed 60 controlled coughs on each study day. Average whole lung clearance through 1 and 2h after administration of salmeterol (42 microg) or placebo via metered dose inhaler (double-blinded, crossover design study) showed no significant difference between treatments. Similarly, for the specific period when cough was added to mucociliary clearance, there was no difference on whole lung clearance between treatments. However, when clearance from the peripheral region of the lung was assessed over the entire 2h period of observation, salmeterol provided a 30% enhancement of airway clearance compared to placebo, average peripheral 2h clearance (%) = 22 +/- 9 vs. 17 +/- 10 for salmeterol vs. placebo (P = 0.05 by paired analysis). Thus, in addition to its bronchodilating effects, salmeterol acutely enhances peripheral airway clearance of secretions in mild-moderate chronic bronchitis.

Adrenergic beta-Agonists↗
PubMed2005

Role of bronchodilators in chronic obstructive pulmonary disease.

The prevalence of chronic obstructive pulmonary disease (COPD) continues to be on the rise. Bronchodilators are first line agents for the symptomatic management of this disease and have proven to be effective in both stable disease status and exacerbations. The stepwise escalation of therapy for COPD according to severity has been outlined in international guidelines. Different classes of bronchodilators exist. The most experience is available for short-acting beta-agonists and anticholinergics. These agents are mainly recommended for the treatment of mild COPD and for symptomatic patients on an as needed basis. Long-acting beta-agonists and anticholinergics have been developed more recently. They are more convenient to use for patients with advanced disease who require maintenance therapy with bronchodilators, and have been shown in this group of patients to provide superior efficacy compared with short-acting agents. Tiotropium, a long-acting anticholinergic, appears to be particularly powerful and may eventually replace ipratropium as the primary agent for COPD treatment. In contrast, the usage of theophylline, which used to be part of the mainstay of treatment for COPD, has declined, mainly secondary to a narrow therapeutic margin and side effects, but it is inexpensive and still has its role. New agents like phosphodiesterase-4-inhibitors are interesting substances that may become important adjuncts in COPD management, but there is limited experience so far. None of the bronchodilators have been shown to change outcome in COPD, but this issue is under active investigation.

Administration, Inhalation↗
PubMed2005

Minimal clinically important differences in COPD lung function.

The FEV1 is widely used by physicians in the diagnosis, staging, treatment, monitoring, and establishing prognosis for patients with COPD. The MCID is the smallest difference which patients perceive as beneficial and which would mandate a change in patient management. A precise MCID for FEV1 has not been established. In attempt to establish a MCID for predose or trough FEV1, several limitations need to be addressed. There are issues such as reproducibility, repeatability, acceptability, variability, placebo effect, and equipment effects. Patient factors, such as baseline level of FEV1, albuterol reversibility, diurnal variation, influence the results. Nonetheless, using anchoring techniques, a change in pre dose FEV1 of about 100 mL can be perceived by patients, correlates with fewer relapses following exacerbations and is in the range usually achieved with bronchodilators approved for COPD. In the future, consistent reporting of spirometric variables, such as a predose FEV1 and other outcomes, can be incorporated into a more quantitative effort to establish the MCID. Also distributional/statistical methods may be useful in determining the MCID FEV1.

Data Interpretation, Statistical↗
PubMed2005

Combination therapy for chronic obstructive pulmonary disease: clinical aspects.

Anticholinergics and beta-agonists reduce bronchoconstriction through different mechanisms, and there is a long history of combination therapy with short-acting agents in these classes for chronic obstructive pulmonary disease. Such combinations may allow lower doses and thereby improve safety. Oral theophylline has also been combined with short-acting bronchodilators for many years. Most studies, however, show only mild improvements in bronchodilation at the expense of increased adverse effects. Professional society guidelines recommend that as the symptoms of chronic obstructive pulmonary disease progress, the patient should receive regular treatment with one or more long-acting bronchodilators, and an inhaled corticosteroid if the patient has repeated exacerbations. The combination of a short-acting anticholinergic with a long-acting beta-agonist, or the combination of a long-acting anticholinergic with a short- or long-acting beta-agonist, has been shown in most studies to improve lung function versus monotherapy with the individual components. Systematic reviews have concluded that fluticasone and salmeterol, and budesonide and formoterol, are superior to placebo and lead to clinically meaningful improvements in lung function, exacerbation rate, and quality of life. Effects on survival are less clear. Some of the other issues to be resolved are the safety of combination therapy, its pharmacoeconomic impact, and the role of newer agents.

Administration, Inhalation↗
PubMed2005

A sarcoidosis genetic linkage consortium: the sarcoidosis genetic analysis (SAGA) study.

BACKGROUND: Sarcoidosis, a systemic granulomatous disease of unknown etiology, likely results from an environmental insult in a genetically susceptible host. In the United States of America, African Americans have a higher sarcoidosis incidence and suffer greater morbidity than Caucasians. METHODS: A sarcoidosis genetic linkage study consortium was established to recruit African-American affected sib pair (ASP) families to identify chromosomal regions that may harbor sarcoidosis susceptibility genes and to determine if environmental factors modify any genetic effects. RESULTS: We successfully met our goal of enrolling 359 ASPs using a multifaceted recruitment approach. In the total 559 sib pairs that were enrolled, genetic analyses revealed incorrectly specified relationships that required reclassification or removal from the analysis dataset of 10.4% of reported full and 1.4% of reported half sib pairs. The final study sample comprised 415 full and 104 half sib pairs with complete data. This included 338 ASPs. Within sib pairs, affection status was not associated with sex. Only 15 per cent of the 229 families had three or more affected sibs, but they contributed 42 per cent of the ASP total. CONCLUSIONS: The SAGA study experience should provide useful lessons and information to serve others in conducting genetic studies of complex diseases in African-American families.

Black or African American↗
PubMed2004

Health-related quality of life of persons with sarcoidosis.

STUDY OBJECTIVES: To describe the health-related quality of life (HRQL) and mental health of persons with sarcoidosis, as well as to assess physician-patient agreement about the presence of sarcoidosis symptoms. DESIGN AND SETTING: Cross-sectional study at three university medical center outpatient pulmonary clinics. PATIENTS: One hundred eleven outpatients with sarcoidosis seen between March and July 2002. MEASUREMENTS: The HRQL of sarcoidosis patients was measured using generic and respiratory disease-specific forms (ie, Medical Outcomes Study 36-item short form survey [SF-36] and the St. George respiratory questionnaire [SGRQ], respectively). Depression was assessed using the Center for Epidemiologic Studies depression scale, and stress was assessed with the perceived stress scale four-item questionnaire. The kappa-statistic was calculated to compare physician-patient agreement in assessing sarcoidosis-related symptoms. RESULTS: Patients had moderate-to-severe reductions across all measured domains in perceived HRQL. Those patients who were prescribed oral corticosteroids had lower scores on both the SF-36 and the SGRQ than did those patients who were not. These differences were statistically significant and clinically important. The prevalence of depression was 66%, and that of significant stress was 55%. Spirometry values (FEV(1), 82% predicted; FVC, 86% predicted) were associated neither with HRQL nor with patients' perceived sarcoidosis symptoms, although they were correlated (r = 0.43; p < 0.0001) with physicians' perceptions that patients were symptomatic. Physicians and patients had only fair agreement (kappa-statistic range, 0.24 to 0.36 [by center]) in assessing perceived sarcoidosis symptoms. CONCLUSIONS: Outpatients with sarcoidosis had global reductions in measured HRQL and mental health indexes, although patients receiving therapy with oral corticosteroids had significantly worse HRQL. Experienced physicians based their assessments of patients' sarcoidosis symptoms on measures that were not related to issues of importance to patients. HRQL measurement may provide a unique insight into the impact that sarcoidosis may have on a patient's life that is not captured in traditional physiologic measures.

Adult↗
PubMed2004

Therapeutic responses in asthma and COPD. Bronchodilators.

The presence of acute reversibility to bronchodilators does not distinguish asthma from COPD. Patients with either condition can benefit from bronchodilators, and should be given a trial to assess their response. Some respond with a change in lung volume with less hyperinflation; others improve their forced inspiratory flow and become much more comfortable. The combination of long-acting beta-agonists (LABAs) and inhaled steroids is useful in both conditions. While anticholinergics seem to yield the best results in COPD, some patients with asthma benefit from their use. Tiotropium may be the most effective agent as monotherapy in COPD, but the combination of an inhaled steroid and a LABA may produce similar results in improving lung function. Long-acting bronchodilators are effective agents as monotherapy in COPD, but in asthma should be combined with a controller medication. Short-acting beta-agonists should be used intermittently in asthma, but may be used regularly or combined with an anticholinergic in COPD. The roles of stereoisomers, leukotriene receptor antagonists, and type 4 phosphodiesterase inhibitors in asthma and COPD remain uncertain at this time.

Adrenergic beta-Agonists↗
PubMed2004

Effects of corticosteroids on lung function in asthma and chronic obstructive pulmonary disease.

Both oral and inhaled corticosteroids have clinically significant effects on symptoms, exacerbations, health status, and lung function in asthma, and to a lesser extent in chronic obstructive pulmonary disease (COPD). Change in FEV(1) does not correlate well with functional tests in COPD and may not be the best measure of response to treatment. Inhaled corticosteroids may be beneficial when added to a beta-agonist for treatment of acute asthma, and the efficacy of oral corticosteroids in this setting is well established. Oral corticosteroids inconsistently improve lung function in stable outpatients with COPD. Individual inhaled corticosteroids do not have a marked effect, but the combination of fluticasone propionate and salmeterol and the combination of budesonide plus formoterol seem to improve FEV(1) over treatment with the individual components. In addition, there is convincing evidence for the use of systemic corticosteroids during acute exacerbations of COPD. Some evidence suggests that patients with COPD who respond to corticosteroids have eosinophilic inflammation and other attributes of an asthma phenotype.

Administration, Inhalation↗
PubMed2004

A short-term comparison of fluticasone propionate/salmeterol with ipratropium bromide/albuterol for the treatment of COPD.

BACKGROUND: This is the first comparison of two combination therapies, fluticasone propionate/salmeterol and ipratropium bromide/albuterol (salbutamol), for the treatment of patients with COPD. METHODS: A randomized, double-blind, double-dummy, parallel group, multicenter evaluation of fluticasone propionate/salmeterol 250/50 microg twice daily via DISKUS and ipratropium bromide/albuterol 36/206 microg four times daily via metered-dose inhaler over 8 weeks was conducted at 41 research sites in the US. Morning pre-dose FEV(1), 6-hour serial spirometry, PEF, dyspnea, night-time awakenings, supplemental albuterol use, and patient diary evaluations of symptoms were evaluated. RESULTS: A total of 365 patients with symptomatic COPD were enrolled. The treatment groups were similar in mean age (63.3 and 63.9 years), screening pulmonary function (44.1% and 43.2% of predicted FEV(1)), race (96% and 95% White), and sex distribution (59% and 60% male). Both fluticasone propionate/salmeterol and ipratropium bromide/albuterol improved lung function, symptoms, and supplemental albuterol use compared with baseline. Fluticasone propionate/salmeterol was more effective than ipratropium bromide/albuterol for improvement in morning pre-dose FEV(1), morning PEF, 6-hour FEV(1) area under the curve (AUC(6)), Transition Dyspnea Index (TDI) focal score, daytime symptom score, night-time awakenings, sleep symptoms, and albuterol-free nights (p < or = 0.013). Compared with day 1, at week 8 the FEV(1) AUC(6) significantly increased with fluticasone propionate/salmeterol and significantly decreased with ipratropium bromide/albuterol (p < or = 0.003). The incidence of adverse events was similar between treatment groups, except for a higher incidence of oral candidiasis with fluticasone propionate/salmeterol. CONCLUSIONS: Short-term treatment with the combined inhaled corticosteroid and long-acting beta(2)-adrenoceptor agonist fluticasone propionate/salmeterol resulted in greater control of lung function and symptoms than combined ipratropium bromide/albuterol bronchodilator therapy, in patients with COPD.

Administration, Inhalation↗
PubMed2003

The Sarcoidosis Health Questionnaire: a new measure of health-related quality of life.

The Sarcoidosis Health Questionnaire (SHQ) is a health-related quality-of-life (HRQL) instrument we designed in a two-part study to allow patients to describe their satisfaction with life as it is affected by sarcoidosis. In the Development Study, we created the SHQ from a 151-item pool generated from interviews with 107 patients, a search of the relevant literature, and discussion with sarcoidosis experts. Using clinical impact methodology and the questionnaire responses of a separate group of 149 patients, we reduced the total number of items to 29. The final SHQ has three domains: Daily Functioning, Physical Functioning, and Emotional Functioning. In the Validation Study, performed with a different group of 111 patients, we found that the SHQ had good internal consistency reliability, as well as evidence of content, criterion, and construct validity based on its comparison with other measures of HRQL (Medical Outcomes Study 36-Item short form and the St. George's Respiratory Questionnaire) and of mental health (the Center for Epidemiologic Study-Depression Scale), as well as with clinical variables including spirometry. The SHQ alone was sensitive to differences in HRQL based on the number of involved organ systems. In conclusion, we have developed a self-completed HRQL questionnaire for U.S. patients with sarcoidosis.

Activities of Daily Living↗
PubMed2002

Nontuberculous mycobacteria in women, young and old.

Lady Windermere syndrome is a unique entity within the spectrum of pulmonary NTM diseases. There are differences in several clinical aspects between Lady Windermere syndrome and the classic pulmonary NTM disease, including manifestations, pathogenesis, and natural history. Recently, emerging pieces of information provide a more scientific explanation of why women are more susceptible to this form of infection and how they develop clinical disease. As the result, these patients probably require quite different diagnostic and therapeutic approaches compared with those with the classic presentation. Studies exclusive to LWS are lacking and are absolutely necessary as they will enhance our understanding of, and hence successful management strategies for, this increasingly recognized disease.

Female↗
PubMed2002

A 6-month, placebo-controlled study comparing lung function and health status changes in COPD patients treated with tiotropium or salmeterol.

BACKGROUND: Tiotropium, a once-daily anticholinergic, and salmeterol represent two inhaled, long-acting bronchodilators from different pharmacologic classes. A trial was designed to examine the efficacy and safety of both compounds with multiple outcome measures, including lung function, dyspnea, and health-related quality of life (HRQoL) in patients with COPD. METHODS: A 6-month, randomized, placebo-controlled, double-blind, double-dummy, parallel-group study of tiotropium, 18 microg once daily via dry-powder inhaler, compared with salmeterol, 50 microg bid via metered-dose inhaler, was conducted in patients with COPD. Efficacy was assessed by 12-h monitoring of spirometry, transition dyspnea index (TDI), and the St. George's Respiratory Questionnaire (SGRQ). RESULTS: A total of 623 patients participated (tiotropium, n= 209; salmeterol, n = 213; and placebo, n = 201). The groups were similar in age (mean, 65 years), gender (75% men), and baseline FEV(1) (mean, 1.08 +/- 0.37 L; percent predicted, 40 +/- 12% [+/- SD]). Compared with placebo treatment, the mean predose morning FEV(1) following 6 months of therapy increased significantly more for the tiotropium group (0.14 L) than the salmeterol group (0.09 L; p < 0.01). The average FEV(1) (0 to 12 h) for tiotropium was statistically superior to salmeterol (difference, 0.08 L; p < 0.001). Tiotropium improved TDI focal score by 1.02 U compared with placebo (p = 0.01), whereas there was no significant change in TDI focal score with salmeterol (0.24 U). Tiotropium was superior to salmeterol in improving TDI focal score (p < 0.05). At 6 months, the mean improvement in SGRQ total score vs baseline was tiotropium, - 5.14 U (p < 0.05 vs placebo); salmeterol, - 3.54 U (p = 0.4 vs placebo); and placebo, - 2.43 U. A statistically higher proportion of patients receiving tiotropium achieved at least a 4-U change in SGRQ score compared to patients receiving placebo. Both active drugs reduced the need for rescue albuterol (p < 0.0001). CONCLUSIONS: Tiotropium once daily produces superior bronchodilation, improvements in dyspnea, and proportion of patients achieving meaningful changes in HRQoL compared to twice-daily salmeterol in patients with COPD.

Aged↗
PubMed2002

Improved sputum expectoration following a single dose of INS316 in patients with chronic bronchitis.

UNLABELLED: Uridine 5'-triphosphate (UTP) is a naturally occurring agonist for P2Y(2) receptors on the apical surface of ciliated respiratory epithelium. UTP stimulates salt and water transport and cilia beat frequency in human airway epithelium in vitro. Single, inhaled doses of UTP stimulate mucociliary clearance in conscious, intubated sheep and in patients with mild chronic bronchitis (smokers and former smokers), suggesting that UTP may be useful for obtaining deep-lung sputum specimens suitable for diagnostic purposes. STUDY OBJECTIVE: UTP is being developed for the cytologic diagnosis of lung cancer under the compound number INS316 Solution for Inhalation (Inspire Pharmaceuticals; Durham, NC). Its ability to improve the quality of expectorated sputum was tested in the current study. DESIGN: Placebo-controlled, double-blind, escalating two-period cross-over study. SETTING: Outpatient volunteers. PATIENTS OR PARTICIPANTS: Twenty-six patients with mild chronic bronchitis. INTERVENTION: Patients attempted to expectorate a specimen spontaneously, following a single inhaled dose of INS316 (10 to 180 mg), and following placebo. MEASUREMENTS AND RESULTS: Sputum weight, sputum cell content, spirometry, and oxyhemoglobin saturation. Only 28% of these patients were able to expectorate a macrophage-containing, deep-lung specimen spontaneously or following inhalation of placebo. In contrast, 85% of the patients were able to produce a specimen following inhalation of INS316. The average weight of the sputum expectorated was increased fourfold by placebo and 10-fold by INS316. A mild transient decrease in pulmonary function was observed following INS316 administration. CONCLUSION: A single dose of INS316 safely improves the ability of patients with mild chronic bronchitis to expectorate a deep-lung sputum specimen suitable for cytologic evaluation.

Adult↗