Using Operational Analysis to Improve Access to Pulmonary Function Testing.

Background. Timely pulmonary function testing is crucial to improving diagnosis and treatment of pulmonary diseases. Perceptions of poor access at an academic pulmonary function laboratory prompted analysis of system demand and capacity to identify factors contributing to poor access. Methods. Surveys and interviews identified stakeholder perspectives on operational processes and access challenges. Retrospective data on testing demand and resource capacity was analyzed to understand utilization of testing resources. Results. Qualitative analysis demonstrated that stakeholder groups had discrepant views on access and capacity in the laboratory. Mean daily resource utilization was 0.64 (SD 0.15), with monthly average utilization consistently less than 0.75. Reserved testing slots for subspecialty clinics were poorly utilized, leaving many testing slots unfilled. When subspecialty demand exceeded number of reserved slots, there was sufficient capacity in the pulmonary function schedule to accommodate added demand. Findings were shared with stakeholders and influenced scheduling process improvements. Conclusion. This study highlights the importance of operational data to identify causes of poor access, guide system decision-making, and determine effects of improvement initiatives in a variety of healthcare settings. Importantly, simple operational analysis can help to improve efficiency of health systems with little or no added financial investment.

Birt-Hogg-Dubé syndrome: a large single family cohort.

BACKGROUND: Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant condition characterized by dermatologic lesions, pulmonary manifestations, and renal tumors. The syndrome arises from germline mutations in the folliculin (FLCN) gene. We present findings from the single largest family BHD cohort described to date. Primary objectives were to characterize cystic lung changes on computed tomography (CT) chest scanning and identify features that stratify patients at higher risk of pneumothorax. Secondary objectives entailed description of the following: type and natural history of BHD-associated pneumothorax, pulmonary function characteristics, and relationship between cystic lung changes and pulmonary function. METHODS: The study was a retrospective chart review for a case series of a single family. Over 70 family members of a proband with documented BHD were identified, 68 of which consented to genetic testing. All those with confirmed BHD were offered a clinical assessment by the Medical Genetics and Pulmonary services which included a history, physical exam, complete pulmonary function tests, and computed tomography (CT) scan of the chest and abdomen. RESULTS: Thirty-six individuals had a heterozygous mutation in the FLCN gene (c.59delT). Of these, 100 % (28/28) had pulmonary cysts, 41 % (13/32) had spontaneous pneumothoraces, 26 % (8/31) had kidney cysts, 3 % (1/31) had renal tumors, and 53 % (18/34) had dermatologic manifestations. Recurrent pneumothoraces were common (40 %). Cyst size (OR 3.23, 95 % CI 1.35-7.73) and extent of lower lung zone disease (OR 6.43, 95 % CI 1.41-29.2) were the only findings associated with pneumothorax. The size or extent of cystic disease did not correlate with lung function results. CONCLUSIONS: This is the largest single family cohort of patients with BHD syndrome documented to date. We found that all individuals had pulmonary cysts, pneumothoraces were common, and cyst size and lower lobe predominant disease were associated with pneumothorax. Lung function was generally preserved and not affected by a high cyst burden.

Flow-volume loop abnormality detecting a previously unrecognized right upper lobe tracheal bronchus.

Tracheal bronchus is a rare anatomic variant in which a bronchus originates from the trachea. Patients may be asymptomatic or present with a variety of respiratory symptoms. We present a case of a patient who presented with a history of poorly controlled asthma and a persistent abnormality of the flow-volume loop. Bronchoscopy revealed a tracheal bronchus with narrowed right-sided bronchial orifices. An unrecognized tracheal bronchus may result in serious complications during elective or emergent endotracheal intubation. Spirometry testing may reveal abnormalities of the flow-volume loop associated with altered airflow. Relying on spirometric values without assessing the shape of the flow-volume loop may lead to misdiagnosis and inappropriate management of lung pathology.

Obesity negatively impacts lung function in children and adolescents.

OBJECTIVES: To investigate the relationship between weight status (body mass index [BMI] percentile and BMI z-score) and lung volumes in healthy children and adolescents. HYPOTHESES: We hypothesized that: (a) there would be a significant inverse relationship between age- and sex-specific BMI distribution and functional residual capacity (FRC), and expiratory reserve volume (ERV), respectively; and (b) obese children would have significantly reduced FRC and ERV compared to their non-obese peers. METHODS: The medical records of all individuals who successfully performed pulmonary function testing between 2000 and 2007 at two university children's hospitals were reviewed. Participants were excluded if they had cardiopulmonary, neuromuscular, or chest wall disease. RESULTS: Of 1,469 record reviewed, 327 subjects met study criteria. Percent predicted ERV was lowest in the obese group (P < 0.001) while residual volume (RV) was lowest in the overweight and obese groups (P < 0.001). Underweight participants had a lower percent predicted forced vital capacity (FVC) (P = 0.027) and vital capacity (VC; P = 0.039). Obese participants had the lowest FEV1 /FVC (P < 0.001). A positive linear relationship existed between BMI z-score and percent predicted FVC, VC, and diffusing capacity of carbon monoxide (DLCO ). A negative linear relationship was found between BMI z-score and percent predicted FRC, ERV, RV, and absolute FEV1 /FVC. CONCLUSIONS: Our results show that increasing weight status in children and adolescents is associated with a general reduction in lung volume measurements, which may reflect impaired lung function, increased respiratory symptoms, and decreased functional status.

Identification and validation of nebulized aerosol devices for sputum induction.

BACKGROUND: Induced sputum cell counts are a noninvasive and reliable method for evaluating the presence, type and degree of airway inflammation in patients with asthma. Currently, standard nebulizer devices used for sputum induction in multiple patients are labelled as single-patient devices by the manufacturer, which conflicts with infection prevention and control requirements. As such, these devices cannot feasibly be used in a clinical sputum induction program. Therefore, there is a need to identify alternative nebulizer devices that are either disposable or labelled for multipatient use. OBJECTIVE: To apply validated rigorous, scientific testing methods to identify and validate commercially available nebulizer devices appropriate for use in a clinical sputum induction program. METHODS: Measurement of nebulized aerosol output and size for the selected nebulizer designs followed robust International Organization for Standardization methods. Sputum induction using two of these nebulizers was successfully performed on 10 healthy adult subjects. The cytotechnologist performing sputum cell counts was blinded to the type of nebulizer used. RESULTS: The studied nebulizers had variable aerosol outputs. The AeroNeb Solo (Aerogen, Ireland), Omron NE-U17 (Omron, Japan) and EASYneb II (Flaem Nuova, Italy) systems were found to have similar measurements of aerosol size. There was no significant difference in induced sputum cell results between the AeroNeb Solo and EASYneb II devices. DISCUSSION: There is a need for rigorous, scientific evaluation of nebulizer devices for clinical applications, including sputum induction, for measurement of cell counts. CONCLUSION: The present study was the most comprehensive analysis of different nebulizer devices for sputum induction to measure cell counts, and provides a framework for appropriate evaluation of nebulizer devices for induced sputum testing.

Establishing a normal range for induced sputum cell counts in Western Canada.

BACKGROUND: Induced sputum cell counts are a noninvasive, reliable method for evaluating the presence, type and degree of airway inflammation. Whether current reference values for induced sputum cell counts are applicable in other induced-sputum laboratories, particularly those in Western Canada or at elevated altitude, is not clear. OBJECTIVES: To describe the normal range of induced sputum cell counts in healthy adults in Western Canada. METHODS: A total of 105 healthy nonsmoking adults with normal bronchial responsiveness and no history of lung disease proceeded with sputum induction. Sputum samples were fixed in formalin. RESULTS: Sixty-nine subjects were included in the final analyses. The mean ± SD and median (interquartile range) of the cell counts, respectively, were: total cell count 2.453 ± 2.108, 2.000 (2.512); neutrophils 1.212 ± 1.491, 0.721 (1.016); eosinophils 0.034 ± 0.069, 0.005 (0.043); macrophages 1.050 ± 1.213, 0.696 (1.005); lymphocytes 0.057 ± 0.161, 0.001 (0.049); and bronchial epithelial cells 0.041 ± 0.126, 0.000 (0.027). The respective differential cell percentages were: neutrophils 50.3 ± 23.5, 51.9 (32); eosinophils 1.4 ± 2.3, 0.3 (2); macrophages 43 ± 22.8, 39.3 (32); lymphocytes 2.6 ± 5.2, 0.4 (2.5); and bronchial epithelial cells 2.2 ± 4.8, 0.0 (2.9). Bland-Altman analysis and intraclass correlation coefficients revealed excellent interobserver agreement for measurement of sputum cell types. DISCUSSION: The range of induced sputum cell counts performed in a laboratory in Western Canada in healthy nonsmoking adult subjects was described; cellular distributions were similar to previous studies. This was also the first description of normal values for formalin-fixed induced sputum samples. CONCLUSIONS: These results confirm that current reference values for induced sputum are generalizable across different laboratories, including those in Western Canada and those at elevated altitude, and are also generalizable to formalin-fixed samples, allowing use in the broader Canadian asthma population.

The impact of diurnal variation on induced sputum cell counts in healthy adults.

BACKGROUND: Induced sputum cell counts are a non-invasive, reliable method for evaluating the presence, type, and degree of inflammation in the airways of the lungs. Current reference values for induced sputum cell counts in healthy adults do not account for the effects of circadian rhythm, including diurnal variation. The objective of this study was to describe the diurnal variation in induced sputum cell counts, compared between early morning and late afternoon, in healthy adult individuals. METHODS: 100 healthy adult subjects with no history of lung disease and normal bronchial reactivity proceeded with induced sputum testing at 7 am and 4 pm on different days. The order of testing was randomized. The cytotechnologist preparing and performing the cell counts was blinded to the sample collection time and subject characteristics. RESULTS: 65 subjects were included in the final analyses. There was no significant change in the total and differential sputum cell counts between the 7 am and 4 pm collections. There was good inter-observer agreement with respect to differential sputum cell count interpretation. CONCLUSIONS: This is the largest study to assess the variation in induced sputum cell counts in healthy adult subjects at different times of the day. We found no significant change in total and differential sputum cell counts between the 7 am and 4 pm collection time points. This is in contrast to studies in asthmatics that demonstrated a circadian variation in sputum cell counts and other markers of inflammation, suggesting that fluctuations in airway inflammatory cells during the day are a disease-specific effect.

Effect of incremental exercise on airway and systemic inflammation in patients with COPD.

Airway and systemic inflammation are features of chronic obstructive pulmonary disease (COPD), and there is growing interest in clarifying the inflammatory processes. Strenuous exercise induces an intensified systemic inflammatory response in patients with COPD, but no study has investigated the airway inflammatory and anti-inflammatory responses to exercise. Twenty steroid-naïve, ex-smokers with diagnosed COPD (forced expired volume in 1 s = 66 ± 12%) underwent baseline collection of venous blood and induced sputum followed by an incremental exercise test to symptom limitation 48 h later. Additional venous blood samples were collected following exercise at 0, 2, and 24 h, while induced sputum was collected 2 and 24 h after exercise. Sputum and blood samples were analyzed for differential cell count, CD4(+) and CD8(+) T lymphocytes (serum only), interleukin (IL)-6, IL-8, IL-10, chemokine (C-C motif) ligand 5 (CCL5), and high sensitivity C-reactive protein (serum only). There was an increase in the number of sputum eosinophils (cells/gram, P = 0.012) and a reduction in sputum IL-6 (P = 0.01) 24 h postexercise. Sputum IL-8 and CCL5 were also persistently decreased after exercise (P = 0.0098 and P = 0.0012, respectively), but sputum IL-10 did not change. There was a decrease in serum eosinophils 2 h after exercise (P = 0.0014) and a reduction in serum CCL5 immediately following and 2 h postexercise (P < 0.0001). Both serum eosinophils and CCL5 returned to baseline levels within 24 h. An acute bout of exercise resulted in a significant increase in the number of sputum eosinophils, which may be mediated by serum CCL5. However, there was also a reduction in sputum proinflammatory cytokines, suggesting some anti-inflammatory effect of exercise in the lungs of steroid-naïve patients with COPD.

Evidence-based risk assessment and recommendations for physical activity clearance: respiratory disease.

The 2 most common respiratory diseases are chronic obstructive pulmonary disease (COPD) and asthma. Growing evidence supports the benefits of exercise for all patients with these diseases. Due to the etiology of COPD and the pathophysiology of asthma, there may be some additional risks of exercise for these patients, and hence accurate risk assessment and clearance is needed before patients start exercising. The purpose of this review was to evaluate the available literature regarding the risks of exercise for patients with respiratory disease and provide evidence-based recommendations to guide the screening process. A systematic review of 4 databases was performed. The literature was searched to identify adverse events specific to exercise. For COPD, 102 randomized controlled trials that involved an exercise intervention were included (n = 6938). No study directly assessed the risk of exercise, and only 15 commented on exercise-related adverse events. For asthma, 30 studies of mixed methodologies were included (n = 1278). One study directly assessed the risk of exercise, and 15 commented on exercise-related adverse events. No exercise-related fatalities were reported. The majority of adverse events in COPD patients were musculoskeletal or cardiovascular in nature. In asthma patients, exercise-induced bronchoconstriction and (or) asthma symptoms were the primary adverse events. There is no direct evidence regarding the risk of exercise for patients with COPD or asthma. However, based on the available literature, it would appear that with adequate screening and optimal medical therapy, the risk of exercise for these respiratory patients is low.

CPAP increases exercise tolerance in obese subjects with obstructive sleep apnea.

Obese subjects commonly suffer from exertional dyspnea and exercise intolerance. Preliminary evidence suggests that treatment with nocturnal continuous positive airway pressure (nCPAP) may improve dyspnea in obese patients with obstructive sleep apnea (OSA), but the effect on exercise tolerance is unknown. This study sought to investigate whether nCPAP improves exercise tolerance and exertional dyspnea in obese patients with OSA. Obese patients prescribed nCPAP for moderate/severe OSA and without cardiopulmonary disease were recruited. Patients completed a constant-load exercise test and Baseline and Transitional Dyspnea Index questionnaires (BDI/TDI) at baseline and after one and three months of nCPAP. Primary outcome was change in constant-load exercise time from baseline to one and three months. Secondary outcomes included changes in isotime dyspnea, isotime leg fatigue and BDI/TDI score at one and three months. Fifteen subjects (body mass index = 43 kg m(-2), apnea-hypopnea index = 49(.)hr(-1)) were studied. Constant-load exercise time increased by 2.0 min (40%, p = 0.02) at one month and 1.8 min (36%, p = 0.04) at three months. At one and three months, isotime dyspnea decreased by 1.4 (p = 0.17) and 2 units (p = 0.04), and leg fatigue decreased by 1.2 (p = 0.18) and 2 units (p = 0.02), respectively. BDI/TDI scores were 2.7 (p = 0.001) and 4.5 points (p < 0.001) at one and three months. Peak oxygen consumption and static pulmonary function were unchanged. Nocturnal CPAP improves exercise tolerance and dyspnea in obese patients with OSA. Effects on exercise time and chronic dyspnea were seen after one and three months of nCPAP, while exertional dyspnea was only improved at three months.

Effects of exercise training on physical impairment, arterial stiffness and health-related quality of life in patients with chronic kidney disease: a pilot study.

BACKGROUND: Patients with chronic kidney disease (CKD) have impaired performance in physical tasks, lower health-related quality of life and high cardiovascular morbidity and mortality. Moderate intensity exercise has been shown to provide cardiovascular and metabolic benefits in healthy individuals and patients without CKD. Long-term exercise training is recommended as a vital component in the management of a number of chronic diseases. This randomized controlled pilot project examined the effects of exercise in predialysis CKD patients. METHODS: Ten patients were randomized to 12 months of exercise (EX) and 10 to standard care (CT). We compared the difference between the two groups in physical impairment (VO(2peak) and endurance time [ET]), arterial stiffness (augmentation index [AI]) and health-related quality of life (EuroQol EQ-5D and Short Form-36 questionnaires) (all measured at baseline and 12 months). RESULTS: The difference between EX and CT was statistically significant for VO(2peak) (3.59 ml O(2)/kg/min; 95% CI 0.92, 6.26; P = 0.01), ET (10.97 min; 95% CI 4.34, 17.59; P = 0.003) and AI (-11.7%; 95% CI -18.79, -4.61; P = 0.003). Clinically important changes were noted in EQ-5D and SF-36. CONCLUSIONS: This study suggests that long-term exercise training improves physical impairment, arterial stiffness and health-related quality of life in patients with predialysis CKD. A larger randomized trial is required to examine the impact of exercise on markers of cardiovascular risk and quality of life in predialysis CKD patients.

Exogenous pulmonary surfactant for the treatment of adult patients with acute respiratory distress syndrome: results of a meta-analysis.

INTRODUCTION: The purpose of this study was to perform a systematic review and meta-analysis of exogenous surfactant administration to assess whether this therapy may be useful in adult patients with acute respiratory distress syndrome. METHODS: We performed a computerized literature search from 1966 to December 2005 to identify randomized clinical trials. The primary outcome measure was mortality 28-30 days after randomization. Secondary outcome measures included a change in oxygenation (PaO2:FiO2 ratio), the number of ventilation-free days, and the mean duration of ventilation. Meta-analysis was performed using the inverse variance method. RESULTS: Two hundred and fifty-one articles were identified. Five studies met our inclusion criteria. Treatment with pulmonary surfactant was not associated with reduced mortality compared with the control group (odds ratio 0.97; 95% confidence interval (CI) 0.73, 1.30). Subgroup analysis revealed no difference between surfactant containing surface protein or not - the pooled odds ratio for mortality was 0.87 (95% CI 0.48, 1.58) for trials using surface protein and the odds ratio was 1.08 (95% CI 0.72, 1.64) for trials without surface protein. The mean difference in change in the PaO2:FiO2 ratio was not significant (P = 0.11). There was a trend for improved oxygenation in the surfactant group (pooled mean change 13.18 mmHg, standard error 8.23 mmHg; 95% CI -2.95, 29.32). The number of ventilation-free days and the mean duration of ventilation could not undergo pooled analysis due to a lack of sufficient data. CONCLUSION: Exogenous surfactant may improve oxygenation but has not been shown to improve mortality. Currently, exogenous surfactant cannot be considered an effective adjunctive therapy in acute respiratory distress syndrome.

Lung structural changes in chronic obstructive pulmonary diseases.

Structural changes in COPD are found in the central airways, peripheral airways, lung parenchyma, and pulmonary vasculature. Broadly there are two different pathways leading to the same physiologic phenotype: one centered on the small airways and involving mucosal inflammation and structural change, and the other centered on the parenchyma involving excessive proteolysis and /or disordered repair processes. A highly variable combination of these changes exists in different patients, in part due to genetic factors. The composite picture seen on pulmonary function tests is evidence of over-inflation of the lung, decreased airflow and abnormalities in gas exchange. Earlier stages of the airway disease are associated with more potentially reversible changes, whereas later stages show more collagen deposition and hence irreversibility. Thus a careful assessment of the structural phenotype of subpopulations of COPD patients is likely to lead to optimal categorization for therapeutic trials, and earlier disease is more likely to response to interventions.

A randomized, controlled trial of doxycycline and rifampin for patients with Alzheimer's disease.

OBJECTIVES: To assess whether doxycycline and rifampin have a therapeutic role in patients with Alzheimer's disease (AD). DESIGN: Randomized, triple-blind, controlled trial. SETTING: Three tertiary care and two community geriatric clinics in Canada. PARTICIPANTS: One hundred one patients with probable AD and mild to moderate dementia. INTERVENTION: Oral daily doses of doxycycline 200 mg and rifampin 300 mg for 3 months. MEASUREMENTS: The primary outcome was a change in Standardized Alzheimer's Disease Assessment Scale cognitive subscale (SADAScog) at 6 months. Secondary outcomes were changes in the SADAScog at 12 months and tests of dysfunctional behavior, depression, and functional status. RESULTS: There was significantly less decline in the SADAScog score at 6 months in the antibiotic group than in the placebo group, (-2.75 points, 95% confidence interval (CI)=-5.28 to -0.22, P=.034). At 12 months, the difference between groups in the SADAScog was -4.31 points (95% CI=-9.17-0.56, P=.079). The antibiotic group showed significantly less dysfunctional behavior at 3 months. There was no significant difference in adverse events between groups (P=.34). There were no differences in Chlamydia pneumoniae detection using polymerase chain reaction or antibodies (immunoglobulin (Ig)G or IgA) between groups. CONCLUSION: Therapy with doxycycline and rifampin may have a therapeutic role in patients with mild to moderate AD. The mechanism is unlikely to be due to their effect on C. pneumoniae. More research is needed to investigate these agents.