Biomedical subjects

James K Stoller

Publications and source records attributed to James K Stoller.

At least 37 records · Page 2Linked to original sources

PubMed2005

Estimating FVC from FEV2 and FEV3: assessment of a surrogate spirometric parameter.

BACKGROUND: In the context that accurate measurement of FVC is important in diagnosing airflow obstruction and in assessing restriction, strategies to achieve reliable and accurate FVC measurement have drawn much attention. OBJECTIVES: Because the rate of achieving end-of-test criteria during spirometry has been shown to be low, with resultant under-recording of the FVC, the current study proposes a regression equation for estimating FVC from measured values of the forced expiratory volume in 2 s (FEV2) and forced expiratory volume in 3 s (FEV3). METHODS: The predictive equation for the estimated FVC from volume measurements within the first 3 s of exhalation (estimated FVC3) was generated based on 330 consecutive acceptable spirograms performed in the Cleveland Clinic Foundation Pulmonary Function Laboratory. The equation was applied to an independent validation set comprised of spirometry measurements on 370 different consecutive patients. RESULTS: In the validation spirometry sample, in which the prevalence of obstruction was 34% (based on values of the measured FEV1/FVC compared to National Health and Nutrition Examination Survey III values), the sensitivity, specificity, and positive and negative predictive values of FEV1/estimated FVC3 for obstruction were 93.8%, 89.1%, 81.2%, and 96.9%, respectively. The misclassification rate was 9.2%. In the same cohort, the mean difference (+/- SD) between estimated FVC3 and measured FVC was 24.7 +/- 237 mL. CONCLUSIONS: Given that FVC is frequently under-recorded, with resultant overestimation of FEV1/FVC and underdiagnosis of airflow obstruction, we believe that estimating FVC from FEV2 and FEV3 can offer practical diagnostic advantages.

Aged↗

PubMed2005

Delay in diagnosis of alpha1-antitrypsin deficiency: a continuing problem.

BACKGROUND AND STUDY OBJECTIVES: Alpha1-antitrypsin (AAT) deficiency is common but under-recognized. A 1994 mail survey showed a long delay between the onset of symptoms and the initial diagnosis of AAT deficiency. In 2003, we carried out a similar mail survey of AAT-deficient individuals to determine whether any delay in diagnosis experienced by individuals with a more recent diagnosis had become shorter. We also determined whether individuals living near medical centers with an expressed interest in AAT deficiency experienced shorter diagnostic delays than those living at a distance. METHODS: Results from mail surveys of two different cohorts were compared: a 1994 survey of 304 individuals with severe AAT deficiency and a 2003 survey of 1,953 AAT-deficient individuals. In the 2003 survey cohort, diagnostic delay intervals were analyzed by calendar year of initial diagnosis, rural vs urban residence, visit to a liver or lung specialist within the last year, and living within 50 miles of a medical center with particular expertise in AAT deficiency. One thousand nine hundred fifty-three individuals responded to the 2003 mail survey (37.4%). RESULTS: In the 2003 cohort, the mean +/- SD diagnostic delay was 5.6 +/- 8.5 years, compared with 7.2 +/- 8.3 years for the 1994 cohort (p = 0.002). In the 2003 cohort, younger patients and male patients experienced shorter diagnostic delays than older patients and female patients (p < 0.0001 and p = 0.007, respectively). For example, the delay was 6.5 +/- 8.8 years for those born in the 1940s, as compared with 0.43 +/- 1.08 years for those born after 1980. Neither urban residence nor living near a center with expertise in AAT deficiency were associated with a shortened diagnostic delay interval. CONCLUSIONS: Although these results show some improvement in the mean diagnostic delay in the 9-year period separating the two studies, under-recognition of AAT deficiency persists. Diagnostic delay of AAT deficiency is longer in women and in older individuals. Educational efforts are underway to enhance clinicians' diagnostic suspicion of AAT deficiency and permit earlier diagnosis and attendant benefits.

Adult↗

PubMed2005

Changing patterns of inpatient respiratory care services over a decade at the Cleveland Clinic: challenges posed and proposed responses.

INTRODUCTION: Changing characteristics of hospitalized patients over the last decade have created challenges for all health-care providers in delivering optimal care. In the specific case of respiratory care, trends that hospitalized patients have generally become sicker over time and that average lengths of stay have generally become shorter have posed the challenge of meeting demands for more services delivered with greater immediacy. We undertook the current analysis to assess how the delivery of respiratory care services at a tertiary-care academic medical center, the Cleveland Clinic Foundation Hospital, has evolved over the decade 1991 to 2001. In this observational study, we examined concurrent departmental trends and speculated that the capability to increase clinical activity with maintained or improved clinical outcomes, preserved costs, and a lower turnover rate among respiratory therapists reflects features of the professional environment within our Section of Respiratory Therapy. METHODS: This analysis compares patterns of respiratory care service delivery in two 5-year intervals: from 1991 to 1996 and from 1996 to 2001. Data were collected using a respiratory care information-management system and an inpatient hospital information system, which track the volume and actual cost of services provided. These analyses accounted for the actual time-based cost of the services, including labor (with benefits), necessary equipment and supplies, medications, and equipment maintenance and depreciation. Hospital case-mix index values were determined according to guidelines from the Centers for Medicare and Medicaid Services, as the weighted average of resource allocation scores assigned to diagnosis-related-group categories of hospitalized patients. RESULTS: From 1991 to 2001, there were important expansions in the scope of respiratory care practice by our Section of Respiratory Care, while the volume of respiratory care services delivered per year increased 1.96-fold (from 339,600 to 665,921 services/y). The number of respiratory therapy consults performed yearly, beginning in 1992 when the service was first implemented, rose to over 10,000/y by 2001. At the same time, the cost of respiratory therapy services delivered per patient decreased by 4.2%. Regarding staffing trends, the number of full-time-equivalent employees increased by 50% (from 65 to 97.5). However, the percent turnover rate among respiratory therapists decreased by 2.3-fold (from 11.5% to 5%). In the face of these trends, the hospital mortality rate for patients with diagnosis-related group 088 (high users of respiratory care services) decreased by 53%, and the length of hospital stay for all patients receiving respiratory treatments decreased by 30%. CONCLUSIONS: This analysis shows that trends of growing demands for respiratory care services have been accompanied by generally improving clinical outcomes and favorable retention of respiratory therapists in our section. We believe that a focus on the process of care, including enhanced professionalism, communication, and participation, has permitted a favorable response to these rising demands.

Academic Medical Centers↗

PubMed2005

Impact of an annual retreat on process improvement in a respiratory therapy section.

BACKGROUND: In order to fulfill the mission of providing superb respiratory care, managing respiratory care services requires communication and collaboration. To enhance communication and collaboration in our Section of Respiratory Therapy at the Cleveland Clinic Foundation, and to generate ideas for improvement, since 1996 we have conducted annual retreats for the Section, during which important challenges and opportunities are discussed in a large-group forum. The current report describes the retreat process and outcomes, namely the ideas generated during these retreats and the frequency with which ideas were implemented successfully. METHODS: The annual retreat brings together all clinical specialists, supervisors, and managers in the Section of Respiratory Therapy, along with the medical director of Respiratory Therapy and representatives of the staff from each shift. In advance of the annual half-day retreat, supervisors and clinical specialists are asked to write a brief description of things that need improvement and actionable proposed solutions to these challenges. These documents are reviewed by the supervisors, managers, education coordinator, and medical director, and a list of discussion topics for the retreat is formulated. The retreat day begins with a brief introduction and summary of the year's activities and then encourages open-ended discussions regarding the various topics, with the explicit, repeated goal of generating solutions. Minutes are kept to identify specific action items, a list of which is visited repeatedly throughout the year, to assess progress toward successful completion of each action item. In the current analysis, the primary outcome measures are the number of ideas generated as action items during the retreats and the frequency with which these ideas have been implemented. RESULTS: Over the 8 years of annual retreats, 103 action items have been generated, of which 84% (n = 87) have been successfully implemented or completed. As evidence of the importance of this group-based activity, we cite several examples of suggestions and action items that were felt to uniquely represent group process and wisdom and which were not proposed beforehand by individuals. CONCLUSIONS: On the basis of this experience, we recommend conducting annual respiratory therapy department retreats. We believe the benefits include collective problem-solving in a public forum to identify solutions not advanced by individuals. Also, we believe that the direct communication in such retreats contributes to enhanced morale, further evidence of which is the very low turnover rate among our respiratory therapists during the 8 years in which we have conducted annual retreats.

Concept Formation↗

PubMed2005

A review of alpha-1 antitrypsin deficiency.

Alpha-1 antitrypsin (AAT) deficiency is a common but under-recognized disease. This hereditary disorder is characterized by low levels of AAT, and increased risks of panacinar emphysema at an early age, liver disease, vasculitis and panniculitis. Destruction of lung parenchyma and consequent emphysema result from an imbalance between different inflammatory proteases (in particular, leukocyte elastase), and the major natural antiprotease, AAT. To offer a review of key aspects of this important condition, we present the epidemiology, natural history, and pathogenesis of AAT deficiency and, in the context of recent data and the publication of an international standards document regarding the diagnosis and management of individuals with AAT deficiency, review current therapy of AAT deficiency.

Humans↗

PubMed2004

Severe agitation among ventilated medical intensive care unit patients: frequency, characteristics and outcomes.

OBJECTIVE: To determine the frequency, characteristics and outcomes of severe agitation among ventilated medical intensive care unit (MICU) patients. DESIGN: Prospective cohort study. SETTING: Eighteen-bed MICU in 964-bed tertiary care center. PATIENTS: All ventilated patients, aged 18 years or older and admitted for more than 24 h between January 1, 2001 and May 8, 2001. INTERVENTIONS: None. MEASUREMENTS: Data were collected daily by concurrent chart abstractions. Variables included sociodemographic, clinical, laboratory, pharmacologic and non-pharmacologic interventions, ventilator settings and adverse events. Severe agitation, the main outcome variable, was defined as two or more Motor Activity Assessment Scale (MAAS) scores above 4 in a 24-h period and sedative and/or narcotic doses above the established sedation and analgesia protocol or a combination of two or more sedatives. RESULTS: Twenty-three (16.1%) of 143 enrolled patients exhibited severe agitation. Agitated patients were younger (hazard ratio [HR] 1.32), more likely to be admitted from an outside hospital ICU (HR 2.48), had lower pH (HR 1.55) and PaO(2)/FIO(2) less than 200 mmHg (HR 2.59). Agitated patients had longer MICU stays (median 12 versus 5 days, p<0.0001) and more ventilator days (median 14 versus 6, p<0.0001). Agitated patients were more likely to self-extubate (26% versus 6%, p=0.002). Benzodiazepines, narcotics and neuromuscular blocking agents were administered more frequently and at higher doses, but haloperidol was not. CONCLUSION: Severe agitation occurs commonly in critically ill patients and is associated with adverse events including longer ICU stays, duration of mechanical ventilation and self-extubation.

Adult↗

PubMed2004

The bronchopulmonary pathology of alpha-1 antitrypsin (AAT) deficiency: findings of the Death Review Committee of the national registry for individuals with Severe Deficiency of Alpha-1 Antitrypsin.

To assess the pathological changes in the lungs and liver of 42 individuals who died while enrolled in the Registry of Individuals with Severe Deficiency of Alpha-1 Antitrypsin (AAT), all available histopathologic surgical or postmortem-derived specimens were reviewed by the pathologist member of the Death Review Committee. The underlying cause of death was emphysema in 34 patients and cirrhosis in 2 patients. Slides of lung were graded for emphysema, and liver specimens were graded for fibrosis, using respective pictorial scoring systems. Correlations between the degree of pathological abnormality and clinical features were evaluated. All lungs exhibited severe panacinar emphysema (mean emphysema score, 7.9 +/- 1.06 [standard deviation], where 10 represents the greatest severity) with a lower lobe predominance. Centriacinar emphysema was minimal. No correlation was found between the pathological severity of emphysema and pulmonary function measurements, and no significant correlation was found between the degree of emphysema and the degree of hepatic fibrosis. Mildly increased bronchial gland-to-wall ratio accompanied mild inflammation and goblet cell hyperplasia. There were minimal changes in small airways. Dilatation of membranous bronchioles was a frequent finding; however, bronchiectasis of larger airways was a minor feature in only 6 patients (15%). Airway morphological features did not correlate with the clinical presence of chronic bronchitis or asthma. Although the lack of correlation between liver and lung pathological changes may reflect different pathogenetic mechanisms of liver disease and lung disease, the lack of correlation between emphysema grade and lung function likely reflects the skewed sample in a series of patients with advanced lung disease.

Cause of Death↗

PubMed2004

Teambuilding and leadership training in an internal medicine residency training program.

OBJECTIVE: The purpose of this report is to describe and evaluate the impact of a 1-day retreat focused on developing leadership skills and teambuilding among postgraduate year 1 residents in an internal medicine residency. METHOD: A group of organizers, including members of the staff, the chief medical residents, administrative individuals in the residency office, and an internal organizational development consultant convened to organize an off-site retreat with activities that would provide experiential learning regarding teamwork and leadership, including a "reef survival exercise" and table discussions regarding the characteristics of ideal leaders. In addition, several energizing activities and recreational free time was provided to enhance the interaction and teamwork dimensions of the retreat. To evaluate the impact of the retreat, attendees completed baseline and follow-up questionnaires regarding their experience of the retreat. RESULTS: Attendees universally regarded the retreat as having value for them. Comparison of baseline to postretreat responses indicated that attendees felt that the retreat enhanced their abilities to be better physicians, resident supervisors, and leaders. Follow-up responses indicated significant increases in attendees' agreement that good leaders challenge the process, make decisions based on shared visions, allow others to act, recognize individual contributions, and serve as good role models. Results on the survival exercise indicated a high frequency with which team-based decisions surpassed individual members' decisions, highlighting the importance and value of teamwork to attendees. CONCLUSIONS: Our main findings were that: participants universally found this 1-day retreat beneficial in helping to develop teamwork and leadership skills and the experiential learning aspects of the retreat were more especially highly rated and highlighted the advantages of teamwork. In the context that this 1-day retreat was deemed useful by faculty and residents alike, further study is needed to assess the impact of this learning on actual clinical practice and the durability of these lessons.

Adult↗

PubMed2004

Role of flexible bronchoscopy in immunocompromised patients with lung infiltrates.

STUDY OBJECTIVE: To study the diagnostic role of flexible bronchoscopy (FB) in immunocompromised patients with pulmonary infiltrates. DESIGN: Prospective, observational study. SETTING: Tertiary care hospital. PATIENTS: A total of 104 consecutive non-HIV-infected immunocompromised patients with lung infiltrates in whom FB was performed. METHODS: The primary outcome measure was the diagnostic yield of FB, which was derived as the number of the diagnoses made using FB results divided by all final diagnoses. Final diagnoses were established using data from FB, surgical lung biopsy (SLB), and microbiology and serology testing, and by the clinical response to empiric therapy. We also studied the diagnostic yields of individual sampling procedures such as BAL, transbronchial biopsy (TBB), and protected-specimen brush (PSB) sampling. RESULTS: Overall, 128 diagnoses were made in 104 patients. The overall diagnostic yield of FB was 56.2% (95% confidence interval [CI], 47 to 64%). FB provided at least one diagnosis in 53 of 104 patients (51%; 95% CI, 40 to 62%). FB was more likely to establish the diagnosis when the lung infiltrate was due to an infectious agent (81%; 95% CI, 67 to 90%) than to a noninfectious process (56%; 95% CI, 43 to 67%; p = 0.011). The diagnostic yields of BAL (38%; 95% CI, 30 to 47%) and TBB (38%; 95% CI, 27 to 51%) were similar (p = 0.94). The diagnostic yield of PSB sampling was lower (13%; 95% CI 6 to 24%; p = 0.001) than that of BAL. The combined diagnostic yield of BAL and TBB (70%; 95% CI, 57 to 80%) was higher than that of BAL alone (p < 0.001). Finally, the diagnostic yield of FB with PSB sampling, BAL, and TBB was similar to that of FB with BAL and TBB. The complication rate from FB was 21% (95% CI, 15 to 31%). Minor bleeding (13%) and pneumothorax (4%) were the most common complications. CONCLUSIONS: FB has a high diagnostic yield in immunocompromised patients with pulmonary infiltrates. Based on our results, we recommend performing TBB in these patients, whenever possible.

Adult↗

PubMed2004

Augmentation therapy for alpha(1)-antitrypsin deficiency.

alpha(1)-Antitrypsin (AAT) deficiency is a common but under-recognised condition. Since its first description by Laurell and Eriksson in 1963, significant advances have been made in understanding the genetics, physiology and pathophysiology of this condition. The intravenous administration of purified AAT to AAT-deficient individuals has been shown to confer biochemical efficacy by raising the serum AAT level above an epidemiologically established 'protective threshold' while preserving the biochemical properties and functional capacity of the protease inhibitor. Although the lack of a large randomised controlled trial to date has precluded the definitive demonstration of clinical efficacy of intravenous AAT augmentation therapy, substantial evidence supporting its use in AAT-deficient individuals with moderate airflow obstruction has accumulated. For example, both large observational studies comparing rates of forced expiratory volume decline among recipients of augmentation therapy versus non-recipients have shown slower rates of decline among augmentation therapy recipients, especially those with moderately severe airflow obstruction. Also, some evidence suggests that use of augmentation therapy confers an anti-inflammatory effect. For example, a web-based survey suggested that recipients of augmentation therapy experienced fewer respiratory infections than non-recipients. Despite its high cost, intravenous AAT augmentation therapy remains the only US FDA-approved treatment option for patients with AAT deficiency. Research into new and evolving treatments is currently underway.

Clinical Trials as Topic↗

PubMed2004

Pneumonia due to Cryptococcus neoformans in a patient receiving infliximab: possible zoonotic transmission from a pet cockatiel.

The use of humanized antibody against tumor necrosis factor alpha (TNF-alpha) may increase the risk of various opportunistic infections, including tuberculosis and fungal infections. We report a case of cryptococcal pneumonia in a patient who was taking infliximab for rheumatoid arthritis. A temporally related exposure history raised the possibility that our patient acquired the infection from his pet cockatiel. It seems prudent to advise patients receiving infliximab to avoid exposure to pet avian excreta.

Aged↗

PubMed2004

The effectiveness of respiratory care protocols.

The principles underlying evidence-based practice are that treatments are effective and can offer benefit to patients. At the same time, optimal practice also avoids offering treatments for which evidence of efficacy is not available. In this regard, the goal of respiratory care protocols is to optimize the allocation of respiratory care services by prescribing to each patient treatments likely to confer benefit and avoiding those that do not. As reviewed in this paper, currently available evidence suggests that protocols (1). help minimize unnecessary arterial blood sampling, placement of arterial catheters, and bronchopulmonary hygiene therapies, (2). help optimize the process of weaning patients from mechanical ventilation, (3). help minimize waste of oxygen, (4). allocate respiratory care services better than does physician-directed care.

Clinical Protocols↗

PubMed2004

Respiratory therapists' attitudes about participative decision making: relationship between managerial decision-making style and job satisfaction.

BACKGROUND: Studies of non-health-care work environments indicate that non-managerial employee job satisfaction is higher in companies that use participative (as opposed to autocratic) decision making. It has not been determined whether managerial decision-making style influences job satisfaction among respiratory therapists (RTs) and which managerial decision-making style RTs prefer. METHODS: We surveyed Nebraska RTs' attitudes regarding their job satisfaction, their perceptions of their managers' decision-making styles (autocratic, consultative, and/or delegative), and which decision-making style they would prefer their managers to use. We sought to determine whether there is a significant correlation between RTs' perceptions of their managers' decision-making styles and the RTs' job satisfaction. The study population was 792 licensed and practicing non-managerial RTs in Nebraska, from which we randomly selected 565 RTs to survey. The self-administered, descriptive survey used 2 Likert scales (one for decision-making style and one for job satisfaction) and inquired about 57 items. The survey was mailed on October 1, 1999. On October 28, 1999, we sent a second mailing to RTs who had not responded. RESULTS: We received 271 responses (response rate 47.9%). The respondents were generally satisfied with their jobs (mean +/- SD Minnesota Satisfaction Questionnaire score 73.46 +/- 11.63). The sub-scale scores ranged from 20 ("very dissatisfied") to 100 ("very satisfied"). The respondents did not want autocratic managerial decision making (mean +/- SD autocratic sub-scale score 4.29 +/- 0.60). Autocratic decision making was associated with lower job satisfaction (r = 0.49), whereas consultative and delegative decision making were associated with higher job satisfaction (r = -0.31 and -0.48, respectively). RTs who worked in departments that had < 25 RT employees reported higher job satisfaction than did RTs in larger departments (p = 0.029). CONCLUSIONS: Our survey data indicate that (1) RTs prefer delegative and consultative managerial decision making, (2) job satisfaction was highest in departments that had < 25 RTs in the department and in which the manager practiced participative decision making. These findings offer guidance for organizing optimal work environments for RTs.

Attitude of Health Personnel↗

PubMed2004

Quality-assurance research: studying processes of care.

To conduct a successful research study, several criteria must be satisfied: the research question must be important (not only to the investigators but to clinicians and managers in other institutions); the research question must be answerable with the available resources; the investigators must be motivated and capable; and the research setting must be appropriate for the study (the institution must have a supportive culture and analytical resources, and the local institutional review board must approve the proposed study). Quality-assurance (QA) research poses some special challenges and requirements. First, although QA studies should be hypothesis-driven, they are usually before-and-after studies, rather than randomized controlled trials. Second, in before-and-after studies the investigators must address and minimize several possible sources of bias that could confound the results. For example, the compared groups must be similar in important features that could affect development of the outcome(s) of interest, and clinical practices other than the practice change that is being tested during the study must be shown not to independently affect the outcome(s) of interest. We discuss several examples of QA studies, and we offer a checklist for the process of considering, designing, executing, presenting, and publishing a QA study.

Health Services Research↗

PubMed2004

Impact of a program to provide patients with comparative information about providers of durable medical equipment for home respiratory care.

BACKGROUND: How patients are informed regarding their choices of durable medical equipment (DME) providers for home-going respiratory equipment may affect their decisions about which vendor to use. When a new enhanced information program to inform home-going patients about all available respiratory DME providers was implemented, we hypothesized that patients' utilization of providers would change and that satisfaction with service would be enhanced. METHODS: The enhanced information program consisted of offering detailed descriptions of the many available providers to home-going patients. To characterize available providers, we administered a questionnaire to all respiratory DME providers listed in our area. We assembled information about the scope of services, the number and types of providers, the geographic range of service, and the providers' contact information, on a 1-page information sheet about the DME providers, which was given to all home-going patients. Case managers, who routinely help patients make such DME arrangements, were oriented about the questionnaire and given the information sheets to distribute. The study compared responses from Medicare insurees prescribed to receive home-going respiratory care equipment on discharge from The Cleveland Clinic Hospital during the periods before and after implementing the enhanced information program. Consecutive eligible patients in the before and after groups were called by two of the study investigators (ERH, DAM), at least 2 weeks after discharge, and, on their granting consent, were asked to complete a telephone survey. RESULTS: Responses were available from 75 patients in each group. Both before and after implementing the enhanced information program, patients' satisfaction with their respiratory DME service providers' services was high. The number of providers selected increased after the program from 12 to 18, and though the differences between the before and after scores were not statistically significant, there was a trend toward prompter visits to patients in their homes by DME-provider respiratory therapists. CONCLUSIONS: The enhanced information program was associated with a larger number of DME providers being selected, with preservation of a high level of patient satisfaction with DME services. The trend toward prompter respiratory therapists' visits to the home and better availability of oxygen canisters for at-home patients suggested benefits from the enhanced information program.

Aged↗

PubMed2004

Pulmonary venous thrombosis and infarction complicating pulmonary venous stenosis following radiofrequency ablation.

Pulmonary vein stenosis is a recently described complication of radiofrequency ablation. We report a patient who experienced thrombosis of the lingular vein and pulmonary infarction resulting from mild single-vessel pulmonary vein stenosis. This report extends available experience with complications of radiofrequency ablation, by demonstrating pulmonary venous thrombosis as a complication of relatively minor (approximately 50% luminal narrowing) stenosis of a single pulmonary vein, despite the fact that the patient was taking an anticoagulant. .

Adult↗

PubMed2003

Cost-effectiveness analysis of augmentation therapy for severe alpha1-antitrypsin deficiency.

A Markov-based decision model was created to assess the cost-effectiveness of augmentation therapy (Aug) for severe alpha1-antitrypsin deficiency, comparing strategies of: (1) no Aug, (2) Aug for life, and (3) Aug until FEV1 is below 35% predicted. A hypothetical cohort of 46-year-old patients with FEV1 49% predicted was followed over time using Monte Carlo simulation across five possible health states: (1) FEV1 50 to 79% predicted, (2) FEV1 35 to 49% predicted, (3) FEV1 below 35% predicted, (4) status-post-lung transplantation, and (5) dead. Treatment for life yielded 7.19 quality-adjusted life-years (QALYs) and cost 895,243 dollars. Treating until FEV1 is below 35% predicted cost 511,930 dollars and produced 6.64 QALYs. "No Aug" cost 92,091 dollars with 4.62 QALYs. The incremental cost-effectiveness ratio was 207,841 dollars/QALY for Aug until FEV1 is below 35% predicted and 312,511 dollars/QALY for the "Aug for life" strategy. In all sensitivity analyses, the incremental cost-effectiveness ratio for Aug for life exceeded 100,000 dollars. The cost of Aug needed to be reduced from 54,765 dollars to 4,900 dollars for the "Aug for life" strategy to be considered cost-effective. We conclude that, compared with other conventionally used health interventions, Aug is relatively less cost-effective. These results should encourage the development of more clinically and cost-effective therapies for alpha1-antitrypsin deficiency.

Cost-Benefit Analysis↗

PubMed2003

Asthma features in severe alpha1-antitrypsin deficiency: experience of the National Heart, Lung, and Blood Institute Registry.

STUDY OBJECTIVES: To describe asthma features in a cohort with alpha(1)-antitrypsin (AAT) deficiency, and determine the impact of asthma on FEV(1) decline. BACKGROUND: Asthma may be common in those with AAT deficiency, and may lead to accelerated airflow obstruction. DESIGN: Analysis of data obtained from a 5-year, prospective National Heart, Lung, and Blood Institute registry. SETTING: A multicenter registry consisting of 37 clinical centers, a central phenotyping laboratory, and a data analysis center. PARTICIPANTS: A cohort of 1,052 subjects with AAT deficiency. MEASUREMENTS AND RESULTS: Asthma was defined as reversible airflow obstruction, recurrent attacks of wheezing, and a reported diagnosis of asthma or allergy with or without an elevated serum IgE level. FEV(1) decline was calculated by least-square means with adjustments for covariables. Asthma was present in 21% of the cohort and in 12.5% of those with a normal FEV(1). Attacks of wheezing were reported in 66%, the first attack occurring at a mean +/- SD age of 31 +/- 16 years. Allergy and asthma was reported in 29% and 38%, respectively. An elevated IgE level occurred in 17% and was significantly associated with signs and symptoms of asthma and an allergy history. Unadjusted FEV(1) decline was less in the group without asthma and a normal IgE level (- 48.5 mL/yr) vs the groups with asthma features (> or = 64 mL/yr) [p = 0.002]. Multivariable analysis showed that bronchodilator response, age, and smoking were significant predictors for FEV(1) decline but not asthma. CONCLUSIONS: Symptoms and signs of asthma are common in AAT deficiency and may start at the age of most rapid FEV(1) loss. Adjusting for other risk factors such as bronchodilator response, asthma as defined does not lead to an accelerated FEV(1) decline. In AAT deficiency, augmentation therapy is not more effective in preventing the loss of lung function in those with asthma compared to those without.

Adult↗