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contemporary reviews in sleep medicine 
Jagan A. Pillai, MBBS, PhD; James B. Leverenz, MD
Topics: ,

Sleep abnormalities are clearly recognized as distinct clinical symptom of concern in neurodegenerative disorders. Appropriate management of sleep related symptoms has a positive impact on the quality of life of patients with neurodegenerative disorders. This review provides an overview of mechanisms that are currently being considered that tie sleep with neurodegeneration. It appraises the literature regarding specific sleep changes among common neurodegenerative diseases with a focus on Alzheimer’s disease and synucleinopathies (i.e., Parkinson’s disease, dementia with Lewy bodies, multiple system atrophy) that have been better studied. Sleep changes may also serve as markers to identify patients in the preclinical stage of some neurodegenerative disorders. A hypothetical model is postulated founded on the conjecture that specific sleep abnormalities, when noted to increase in severity beyond that expected for age, could be a surrogate marker reflecting pathophysiological processes related to neurodegenerative disorders. This provides a clinical strategy for the screening of patients in the preclinical stages of neurodegenerative disorders to enable therapeutic trials to establish efficacy of neuroprotective agents to prevent or delay the development of symptoms and functional decline. It is unclear if sleep disturbance directly impacts neurodegenerative processes or is a secondary outcome of neurodegeneration; this is an active area of research. The clinical importance of recognizing and managing sleep changes in neurodegenerative disorders is beyond doubt.

topics in practice management 
Lawrence Ward, MD MPH FACP; Rhea E. Powell, MD MPH; Michael L. Scharf, MD; Andrew Chapman, DO; Mani Kavuru, MD
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Healthcare is at a crossroads, under pressure to add value by improving patient experience and health outcomes and reducing costs to the system. Efforts to improve the care model in primary care, such as the patient-centered medical home, have enjoyed some success. Yet primary care accounts for only a small portion of total healthcare spending, and there is a need for policies and frameworks to support high quality, cost-efficient care in specialty practices of the “medical neighborhood”. The Patient-Centered Specialty Practice (PCSP) model offers ambulatory-based specialty practices one such framework, supported by a formal recognition program through the National Committee for Quality Assurance. The key elements of the PCSP include processes to support timely access to referral requests, improved communication and coordination with patients and referring clinicians, reduced unnecessary and duplicative testing, and an emphasis on continuous measurement of quality, safety and performance improvement for a population of patients. Evidence to support the model remains limited, and estimates of net costs and value to practices are not fully understood. The PCSP model holds promise for promoting value-based healthcare in specialty practices. The continued development of appropriate incentives are required to ensure widespread adoption.

original research 
Huimin Wu, MD; Robert A. Wise, MD; Ann E. Medinger, MD
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Background  Guidelines recommend the confirmation of a COPD diagnosis with spirometry. ICD-9-CM diagnostic codes are used frequently to identify patients with COPD for administrative purposes. However, coding the diagnosis of COPD does not require spirometric confirmation. The purpose of this study was to determine how often the discharge diagnoses of COPD is supported by spirometric measurements in the VA health system.

Methods  We reviewed records of patients hospitalized for COPD in a VA teaching hospital between 2005 and 2015. Individuals were counted once; rehospitalizations for COPD in the same time frame were excluded. Patients’ records were assessed for presence of spirometric measurements and for spirometric evidence of COPD.

Results  There were 1278 discharges with the principal diagnosis of COPD and allied conditions in the time frame. A total of 826 discharged-patients were included. Among them, 21% had no spirometric measurements, 12% were unable to perform the breathing maneuvers correctly, 56% had spirometric evidence of airways obstruction and 11% had normal pre or post bronchodilator FEV1/FVC measurements. Older patients were more likely to fail the spirometry or have no documented spirometry. Younger patients were more likely to have the first spirometry after their COPD hospitalizations.

Conclusions  Caution must be taken when using the discharge diagnosis database to measure health care outcomes and determine resource management. Efforts are needed to assure that patients clinically suspected to have COPD are tested with spirometry to improve the accuracy of diagnosis of COPD.

original research 
Yue-Nan Ni; Jian Luo; He Yu; Dan Liu; Ni Zhong; Jiangli Cheng; Bin-Miao Liang; Zong-An Liang
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Background  The effects of high flow nasal cannula (HFNC) on adult patients with acute respiratory failure (ARF) are controversial. We aimed to further determine the effectiveness of HFNC in reducing the rate of endotracheal intubation in adult patients with ARF by comparison to noninvasive positive pressure ventilation (NIPPV) and conventional oxygen therapy (COT).

Methods  The Pubmed, Embase, Medline, Cochrane Central Register of Controlled Trials (CENTRAL) as well as the Information Sciences Institute (ISI) Web of Science were searched for all the controlled studies that compared HFNC with NIPPV and COT in adult patients having ARF. The primary outcome was the rate of endotracheal intubation and the secondary outcomes were intensive care unit (ICU) mortality and length of ICU stay (ICU LOS).

Results  Eighteen trials with a total of 3881 patients were pooled in our final studies. Except for ICU mortality (I2=67%, χ2=12.21, P=0.02) and rate of endotracheal intubation (I2=63%, χ2=13.51, P=0.02) between HFNC and NIPPV, no significant heterogeneity was found in outcome measures. Compared with COT, HFNC was associated with a lower rate of endotracheal intubation (Z=2.55, P=0.01), while no significant difference was found in the comparison with NIPPV (Z=1.40, P=0.16). As for the ICU mortality and ICU LOS, HFNC did not show any advantage over either COT or NIPPV.

Conclusions  In patients with ARF, HFNC is a more reliable alternative of NIPPV to reduce rate of endotracheal intubation than COT.

original research 
Adrian Ceccato, MD; Antoni Torres, MD, PhD; Catia Cilloniz, PhD; Rosanel Amaro, MD; Albert Gabarrus, MSc; Eva Polverino, MD, PhD; Elena Prina, MD; Carolina Garcia- Vidal, MD, PhD; Eva Muñoz-Conejero, PhD; Cristina Mendez, MD; Isabel Cifuentes, MD; Jorge Puig de la Bella Casa, MD; Rosario Menendez, MD, PhD;; Michael S. Niederman, MD.
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Objectives  The burden of pneumococcal disease is measured only through patients with invasive pneumococcal disease. The urinary antigen test (UAT) for pneumococcus has exhibited a high sensitivity and specificity. We aimed to compare the pneumococcal pneumonias diagnosed as invasive disease with pneumococcal pneumonias defined by UAT.

Methods  Prospective observational study on consecutive non-immunosuppressed patients with community-acquired pneumonia from January 2000 to December 2014. Patients were stratified in 2 groups: Invasive pneumococcal pneumonia (IPP) defined as a positive blood culture or pleural fluid culture and non-invasive pneumococcal pneumonia (NIPP) defined as a positive UAT with blood or pleural fluid culture negative.

Results  We analyzed 779 (15%) patients out of 5,132 where 361 (46%) had IPP and 418 (54%) were NIPP. Compared with IPP cases, the NIPP cases presented more frequent chronic pulmonary disease and received previous antibiotics more frequently. IPP patients presented more severe CAP, higher inflammatory markers and worse oxygenation at admission, more pulmonary complications, greater extrapulmonary complications, longer time to clinical stability and longer length of hospital stay compared to NIPP group. Age, chronic liver disease, mechanical ventilation and acute renal failure were independent risk factors for 30-day crude mortality. Neither IPP nor NIPP were an independent risk factor for 30-day mortality.

Conclusions  A high percentage of confirmed pneumococcal pneumonia is diagnosed by UAT. Despite differences in clinical characteristics and outcomes, IPP is not an independent risk factor for 30-day mortality compared with NIPP, reinforcing the importance of NIPP for pneumococcal pneumonia.

original research 
James D. Mancuso, M.D., Dr.P.H.; Rupal M. Mody, M.D.; Cara H. Olsen, Dr.P.H.; Lee H. Harrison, M.D.; Mathuram Santosham, M.D.; Naomi E. Aronson, M.D.
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Background  Bacille Calmette-Guérin vaccination (BCG) is known to cause false positive tuberculin skin test (TST) results from cross-reactions to mycobacterial antigens. However, the duration of BCG influence on the TST is poorly characterized. The objective of the study was to assess the long-term effect of BCG vaccination on TST reactivity.

Methods  Data on TST reactivity were prospectively collected during 1935-47 as part of a clinical trial among American Indians / Alaskan Natives and retrospectively thereafter between 1948 and 1998. TST induration of > 10 millimeters was defined as positive. Kaplan-Meier and multivariate Cox regression were used to compare the time to TST conversion and reversion between the BCG and placebo groups.

Results  BCG vaccination after infancy was associated with an increased risk of TST reactivity in the first 15 years after vaccination (adjusted Hazard Ratio=2.33). This association remained during the interval 16-55 years after vaccination, although the effect was attenuated (adjusted Hazard Ratio=1.26). Age at vaccination modestly impacted the effect of BCG on TST in the first 15 years. Positive TSTs among the BCG-vaccinated group were more likely to revert to negative during the first 15 years but not in the latter period.

Conclusions  This study provides evidence that BCG vaccination after infancy may influence the TST beyond the 10-year period conventionally accepted by the Centers for Disease Control and Prevention (CDC), extending up to 55 years after vaccination. This suggests that BCG vaccination should be taken into account when interpreting TST results regardless of time elapsed since vaccination.

original research 
Rafael Mesquita, MSc, PT; Nienke Nakken, MSc; Daisy J.A. Janssen, MD, PhD; Esther H.A. van den Bogaart, MSc; Jeannet M.L. Delbressine, BSc; Johannes M.N. Essers, MSc; Kenneth Meijer, PhD; Monique van Vliet, MD; Geeuwke J. de Vries, MD, PhD; Jean W.M. Muris, MD, PhD; Fabio Pitta, PhD, PT; Emiel F.M. Wouters, MD, PhD, FERS; Martijn A. Spruit, PhD, PT, FERS
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Background  Resident loved ones of patients with COPD can play an important role in helping patients to engage in physical activity. We aimed to compare activity levels and exercise motivation between COPD patients and their resident loved ones; to compare the same outcome measures in patients after stratification for the physical activity level of the loved ones; and to predict the likelihood of being physically active in patients with a physically active resident loved one.

Methods  125 patient-loved one dyads were cross-sectionally and simultaneously assessed. Sedentary behaviour, light activities and moderate-to-vigorous physical activity (MVPA) were measured with a triaxial accelerometer during free-living conditions for at least 5 days. Five exercise motivation constructs were investigated: amotivation, external regulation, introjected regulation, identified regulation, and intrinsic regulation.

Results  Patients spent more time in sedentary behaviour and less time in physical activity than their loved ones (P<0.0001). More intrinsic regulation was observed in loved ones compared to patients (P=0.003), with no differences in other constructs. Despite similar exercise motivation, patients with an active loved one spent more time in MVPA (mean (95% CI) 31 (24, 38) vs 18 (14, 22) min·day-1; P=0.002) and had a higher likelihood of being active (OR (95% CI) 4.36 (1.41, 13.30); P=0.01) than patients with an inactive loved one after controlling for age, body mass index and degree of airflow limitation.

Conclusions  COPD patients are more physically inactive and sedentary than their loved ones, despite relatively similar exercise motivation. Nevertheless, patients with an active loved one are more active themselves and have a higher likelihood of being active.

original research 
Anthony De Soyza; Melissa J. McDonnell, MD; Pieter C. Goeminne, MD, PhD; Stefano Aliberti, MD, PhD; Sara Lonni, MD; John Davison, RN; Lieven J. Dupont, MD, PhD; Thomas C. Fardon, MD; Robert M. Rutherford, MD; Adam T. Hill, MD; James D. Chalmers, MD PhD
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Introduction  We studied if Bronchiectasis (BR) and Rheumatoid arthritis (RA) when manifesting as an overlap syndrome (BROS) was associated with worse outcomes than other BR aetiologies applying the Bronchiectasis Severity Index (BSI).

Methods  We interrogated the Bronchiectasis Severity Index (BSI) databases of 1716 patients across 6 centres: Edinburgh, UK (608 patients), Dundee, UK (N=286), Leuven, Belgium (N=253), Monza, Italy (N=201), Galway Ireland (N=242) and Newcastle, UK (N=126). Patients were categorised as BROS (those with RA and Bronchiectasis without interstitial lung disease), idiopathic bronchiectasis, Bronchiectasis-COPD overlap syndrome (BCOS) and “other” BR aetiologies. Mortality rates, hospitalisation and exacerbation frequency were recorded.

Results  We identified 147 patients with BROS (8.5% of cohort). There was a statistically significant relationship between BROS and mortality although this was not associated with higher rates of bronchiectasis exacerbations or bronchiectasis-related hospitalisations. The mortality rate over a mean of 48 months was 9.3% for idiopathic BR, 8.6% in patients with “other” causes of BR, 18% for RA and 28.5% for BCOS. Mortality was statistically higher in BROS and BCOS compared with all other aetiologies. The BSI scores were statistically but not clinically significantly higher in those with BROS when compared to idiopathic BR (BSI mean 7.7 vs. 7.1 respectively, p <0.05). BCOS had significantly higher BSI scores (mean 10.4), Pseudomonas aeruginosa colonization rates (24%) and prior hospitalisation rates (58%).

Conclusions  Both BROS and BCOS groups have an excess of mortality -the mechanisms for this may be complex but these data highlight that these subgroups require additional study to understand this excess mortality.

evidence-based medicine 
Anne B. Chang, FRACP, PhD; John J. Oppenheimer, MD; Miles M. Weinberger, MD, FCCP; Bruce K. Rubin, FRCPC, MD; Kelly Weir, PhD; Cameron C. Grant, FRACP, PhD; Richard S. Irwin, MD, Master FCCP

Background  Using management algorithms or pathways potentially improves clinical outcomes. We undertook systematic reviews to examine various aspects in the generic approach (use of cough algorithms and tests) to the management of chronic cough in children (aged ≤14-years) based on key questions using the PICO format.

Methods  We used the CHEST expert cough panel’s protocol for the systematic reviews and the American College of Chest Physicians (CHEST) methodological guidelines and GRADE framework. Data from the systematic reviews in conjunction with patients’ values and preferences and the clinical context were used to form recommendations. Delphi methodology was used to obtain the final grading.

Results  Combining data from systematic reviews addressing 5 key questions, we found high quality evidence that a systematic approach to the management of chronic cough improves clinical outcomes. While there was evidence from several pathways, the highest evidence was from the use of the CHEST approach. However, there was no or little evidence to address some of the key questions posed.

Conclusion  Compared to the 2006 Cough Guidelines, there is now high quality evidence that in children aged ≤14 years with chronic cough (>4 weeks duration); the use of cough management protocols (or algorithms) improves clinical outcomes and; cough management or testing algorithm should differ depending on the associated characteristics of the cough and clinical history. A chest radiograph and, when age appropriate, spirometry (pre and post β2 agonist) should be undertaken. Other tests should not be routinely performed and undertaken in accordance to the clinical setting and the child’s clinical symptoms and signs (e.g. tests for tuberculosis when child has been exposed).

original research  OPEN ACCESS
Pu Liao, MD; Jean Wong, MD; Mandeep Singh, MBBS; David T. Wong, MD; Sazzadul Islam, MS; Maged Andrawes, MD; Colin M. Shapiro, FRCPC; David P. White, MD; Frances Chung, MBBS; Frances Chung
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Background  Surgical patients with obstructive sleep apnea (OSA) are at increased risk for perioperative complications. Postoperative supplemental oxygen is commonly used but it may contribute to respiratory depression in OSA patients receiving opioids. The objective of the study is to investigate the effect of postoperative supplemental oxygen on SaO2, sleep respiratory events, and CO2 level in patients with untreated OSA.

Methods  Consented patients with an apnea hypopnea index (AHI) >5 events/h on a preoperative polysomnography were randomized (1:1) to oxygen (O2) or no oxygen (Control). Oxygen group received O2 at 3 l/min via nasal prongs for 3 postoperative nights. The primary outcomes were polysomnographic parameters measuring SaO2, sleep respiratory events, and PCO2 measured by transcutaneous CO2 monitor (PtcCO2) on night 1-3. The intention-to-treat and per protocol analysis were done.

Results  123 patients were randomized; O2-group:62, and Control-group:61. On night-3, the O2 vs. Control-group had a higher average SaO2: 95.2±3% vs. 91.4±4% (p<0.001) and lower oxygen desaturation index: 2.3(0.2, 13.8) vs. 18.5(8.2, 45.9) events/h [median (25th,75th percentile), p<0.0001]. The O2 group had a decreased AHI, 8.0(2.1, 19.9) vs, 15.6(9.5, 45.8) (p=0.016) ; hypopnea index (p<0.001), central apnea index (p=0.026) and a shortened longest apnea-hypopnea duration (p=0.002). Although PtcCO2-CT55 ≥ 10% on postoperative night 1, 2 or 3 was found in 11.4% patients, there was no difference in PtcCO2 between the groups.

Conclusions  Postoperative supplemental O2 was found to improve oxygenation and decrease AHI without increasing the duration of apnea-hypopnea event or PtcCO2 level. A small number of patients had significant CO2 retention while receiving supplemental O2.

original research 
Philip H. Quanjer, MD, PhD; Gregg L. Ruppel, MEd; Arnulf Langhammer, MD PhD; Abhishek Krishna, MD; Frans Mertens, B ICT; Ane Johannessen, PhD; Ana M.B. Menezes, MD; Fernando C. Wehrmeister, PhD; Rogelio Perez-Padilla, MD; Maureen P. Swanney, PhD; Wan C. Tan, MD; Jean Bourbeau, MD
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Background  Recommendations on interpreting tests of bronchodilator responsiveness (BDR) are conflicting. We investigated the dependence of BDR criteria on sex, age, height, ethnicity and severity of respiratory impairment.

Methods  BDR tests were available from clinical patients in the Netherlands, New Zealand and the USA (N=15,278, 51.7% females) and surveys in Canada, Norway and five Latin-American countries (N=16,250, 54.7% females). BDR in FEV1, FVC and FEV1/ FVC was expressed as absolute change, % baseline, % predicted and z-score.

Results  Change (Δ) in FEV1 and FVC in mL was unrelated to the baseline value but biased towards age, height, sex and level of airways obstruction; ΔFEV1 was significantly lower in African Americans. In 1106 subjects with a low FEV1 (200-1621mL) the FEV1 increased 12-44.7% baseline but <200mL. Expressing BDR as percentage of predicted or z-score attenuated the bias and made the 200mL criterion redundant, but reduced positive responses by half. ΔFEV1 % baseline increased with the level of airflow obstruction but decreased with severe obstruction when expressed as z-scores or % predicted; ΔFVC, however expressed, increased with the level of airflow obstruction.

Conclusions  Expressing FEV1 responsiveness as % baseline spuriously suggests that responsiveness increases with the severity of respiratory impairment. Expressing change in FEV1 or FVC as % predicted or in z-scores eliminates this artefact and renders the required 200mL minimum increase redundant. In severe airways obstruction ΔFVC should be critically evaluated as an index of clinically important relief of hyperinflation, with implications for bronchodilator drug trials.

point and counterpoint 
Anna R. Hemnes, MD
Topics: , , ,
No abstract is available for this article
point and counterpoint 
Anna R. Hemnes, MD
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No abstract is available for this article
point and counterpoint 
Mark Jay Zucker, MD, JD, FACC, FACP, FCCP
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No abstract is available for this article
point and counterpoint 
Mark Jay Zucker, MD, JD, FCCP
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No abstract is available for this article
original research 
Ji An Hwang; Young Sam Kim; Ah Young Leem; Moo Suk Park; Se Kyu Kim; Joon Chang; Ji Ye Jung
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Background  Sarcopenia and osteoporosis are systemic features of chronic obstructive pulmonary disease (COPD). The present study investigated the association between sarcopenia and osteopenia/osteoporosis, and the factors associated with low bone mineral density (BMD) in men with COPD.

Methods  Data of 777 men with COPD who underwent both pulmonary function test and dual energy X-ray absorptiometry were extracted from the Korean National Health and Nutritional Examination Survey database between 2008 and 2011. Sarcopenia was assessed with the appendicular skeletal mass index (ASMI) and osteopenia/osteoporosis with the T-score.

Results  As the severity of airflow limitation increased, sarcopenia prevalence increased (Ptrend<0.001). Additionally, as the degree of sarcopenia became severe, osteopenia/osteoporosis prevalence increased (Ptrend<0.001), and a significant positive correlation was noted between appendicular skeletal muscle mass and BMD (ASMI–T-score: r=0.408, P<0.001). Sarcopenia was independently associated with an increased risk of low BMD in men with COPD (OR=2.31; 95%CI,1.53–3.46; P<0.001). Old age and low fat mass were significantly associated with low BMD in both sarcopenic and non-sarcopenic participants. High serum hemoglobin and insulin levels were associated with a reduced risk of low BMD only in the sarcopenic participants, while exercise and dietary intake were associated with a reduced risk only in the non-sarcopenic participants.

Conclusions  Sarcopenia is closely correlated with osteopenia/osteoporosis in men with COPD. Moreover, different factors are associated with low BMD according to the presence/absence of sarcopenia in that population.

original research 
Donald P. Tashkin, MD; Elizabeth R. Volkmann, MD; Chi-Hong Tseng, PhD; Michael D. Roth, MD; Dinesh Khanna, MD; Daniel E. Furst, MD; Philip J. Clements, MD; Arthur Theodore, MD; Suzanne Kafaja, MD; Grace Hyun Kim, PhD; Jonathan Goldin, MD; Edgar Ariolla, PharmD; Robert M. Elashoff, PhD
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Background  Cough is a common symptom of scleroderma-related interstitial lung disease (SSc-ILD), but its relationship to other characteristics of SSc-ILD, impact on cough-specific QoL and response to therapy for SSc-ILD have not been well studied.

Methods  We investigated frequent cough (FC) in SSc-ILD patients (N=142) enrolled in Scleroderma Lung Study II, a randomized controlled trial comparing mycophenolate mofetil (MMF) and oral cyclophosphamide (CYC) as treatments for ILD. We determined the impact of FC on QoL (Leicester Cough Questionnaire [LCQ]), evaluated change in FC in response to treatment for SSc-ILD, and examined the relationship between gastroesophageal reflux disease (GERD) and cough during the trial.

Results  Study participants who reported FC at baseline (61.3%) reported significantly more dyspnea, exhibited more extensive ILD on HRCT, had a lower diffusing capacity for carbon monoxide (DLCO) and reported more GERD symptoms than those without FC. Cough-specific QoL was modestly impaired in patients with FC (total LCQ score 15.4±3.7; normal range 3-21, higher scores indicating worse QoL). The proportion of patients with FC at baseline declined by 44% and 41% over 2 years in the CYC and MMF treatment arms, respectively, and this decline was significantly related to changes in GERD and ILD severity.

Conclusions  Frequent cough occurs commonly in SSc-ILD, correlates with both the presence and severity of GERD and ILD at baseline and declines in parallel with improvements in both ILD and GERD during a 2-year course of therapy. Frequent cough might serve as a useful surrogate marker of treatment response in SSc-ILD trials.

point and counterpoint 
Charles A. Powell, MD, FCCP
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No abstract is available for this article
point and counterpoint 
John D. Goodson, MD
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No abstract is available for this article
point and counterpoint 
Charles A. Powell, MD, FCCP
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No abstract is available for this article

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  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543