CHEST publishes select peer-reviewed, accepted manuscripts Online First each week. The media embargo is lifted on the date of Online First publication. Final, edited versions will appear in a numbered issue of CHEST and may contain substantive changes. We encourage readers to check back for the final article. Online First papers are indexed in PubMed and by search engines, but the information, including the final title and author list, may be updated on final publication.

original research 
Felipe Cortopassi, PT, RPFT; Bartolome Celli, MD; Miguel Divo, MD; Victor Pinto-Plata, MD
Topics: , , ,

Introduction:  In chronic obstructive pulmonary disease (COPD), a decreased inspiratory/total lung capacity ratio (IC/TLC), is associated with dynamic hyperinflation (DH) and poor exercise capacity. The association to upper extremity force measured by handgrip strength (HGS) and 6 minute walk distance has not been described. We hypothesized that IC/TLC affects muscle strength of upper and lower extremities affecting HGS and the six minute walk test (6MWD) performance.

Methods:  We prospectively measured lung function, HGS and 6MWD in 27 patients with COPD and 12 healthy nonsmoking individuals twice, 1 year apart. The patients were classified according to level of hyperinflation in 2 groups, IC/TLC > or ≤ 25%.

Results:  Patients with COPD had reduced lung function, static hyperinflation, reduced HGS and 6MWD compared to the controls on both evaluations (p < 0.01). There was a statistically significant deterioration in HGS, IC/TLC and 6MWD after 1 year follow up in the COPD compared to the control group (p < 0.001). More hyperinflation (IC/TLC < .25) was associated with lower HGS and 6MWD (p < 0.001). Changes in IC/TLC correlated with changes in HGS (r = 0.429, p < 0.05). A multivariate analysis determined that IC/TLC was an independent factor associated to HSG and to 6MWD.

Conclusion:  Handgrip strength and 6MWD are reduced in patients with COPD, particularly in patients with hyperinflation with evidence of longitudinal deterioration not seen in controls. This suggests that resting hyperinflation may exert a detrimental effect on cardiac function and play a role in the reduced exercise performance in COPD patients.

original research 
Guillaume Dumas, MD; Guillaume Géri, MD; Claire Montlahuc, MD; Sarah Chemam, MD; Laurence Dangers, MD; Claire Pichereau, MD; Nicolas Brechot, MD; Matthieu Duprey, MD; Julien Mayaux, MD; Maleka Schenck, MD; Julie Boisramé-Helms, MD, PhD; Guillemette Thomas, MD; Loredana Baboi, PhD; Luc Mouthon, MD, PhD; Zair Amoura, MD, PhD; Thomas Papo, MD, PhD; Alfred Mahr, MD, PhD; Sylvie Chevret, MD, PhD; Jean-Daniel Chiche, MD, PhD; Elie Azoulay, MD, PhD
Topics: ,

Background:  Systemic rheumatic diseases (SRD) patients may require ICU management for SRD exacerbation, treatment-related infectious or toxicities.

Methods:  Observational study in 10 university-affiliated ICUs in France. Consecutive patients with SRD were included. Determinants of ICU mortality were identified through multivariable logistic analysis.

Results:  363 patients (65.3 % women, median age 59y (IQR, 42-70)) accounted for 381 admissions. Connective tissue disease (primarily Systemic Lupus Erythematosus) accounted for 66.1% of SRD and systemic vasculitides for 26.2 % (chiefly ANCA-associated vasculitides). SRD was newly diagnosed in 43 (11.3%) cases. Direct admission to ICU occurred in 143 (37.9%) cases. Reasons for ICU admissions were infection (39.9%), SRD exacerbation (34.4%), toxicity (5.8 %) or miscellaneous (19.9%). Respiratory involvement was the leading cause of admission (56.8 %), followed by shock (41.5 %) and acute kidney injury (42.2%). Median SOFA on day-1 was 5 [3-8]. Mechanical ventilation was required in 57% cases, vasopressors in 33.9% and renal replacement therapy in 28.1%. ICU mortality rate was 21.0% (80 deaths). Factors associated with ICU mortality were shock (OR: 3.77 [95%CI, 1.93 -7.36]), SOFA score at day 1 (OR: 1.19 [95%CI, 1.10-1.30]) and direct admission (OR: 0.52, [CI 0.28-0.97]. Neither comorbidities nor SRD characteristics were associated with survival.

Conclusions:  In SRD patients, critical care management is mostly needed in patients with previously known SRD; still, diagnosis can be made in the ICU in 12% of the patients. Infection and SRD exacerbation account for more than two-third of the situations, both targeting chiefly the lungs. Direct admission to the ICU might improve outcomes.

original research 
Roop Kaw, MD; Priyanka Bhateja, MD; Hugo Paz y Mar, MD; Adrian V. Hernandez, MD, PhD; Anuradha Ramaswamy, MD; Abhishek Deshpande, MD, PhD; Loutfi S. Aboussouan, MD
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Background:  Among patients with obstructive sleep apnea (OSA) a higher number of medical morbidities are known to be associated with those that have obesity hypoventilation syndrome (OHS) compared to OSA alone. OHS can therefore pose a higher risk of postoperative complications after elective non-cardiac surgery (NCS) and is often unrecognized at the time of surgery. The objective of this study was to retrospectively identify patients with OHS and compare their postoperative outcomes with those who have OSA alone.

Methods:  Patients meeting criteria for OHS were identified within a large cohort of patients with OSA who underwent elective NCS at a major tertiary care center. We identified postoperative outcomes associated with OSA and OHS as well as the clinical determinants of OHS (BMI, AHI). Multivariable logistic or linear regression models were used for dichotomous or continuous outcomes, respectively.

Results:  Patients with hypercapnia from definite or possible OHS, and overlap syndrome are more likely to develop postoperative respiratory failure [OR: 10.9 (95% CI 3.7-32.3), p<0.0001], postoperative heart failure (p<0.0001), prolonged intubation [OR: 5.4 (95% CI 1.9-15.7), p=0.002), postoperative ICU transfer (OR: 3.8 (95% CI 1.7-8.6), p=0.002]; longer ICU (beta coefficient: 0.86; SE: 0.32, p=0.009) and hospital length of stay (beta coefficient: 2.94; SE: 0.87, p=0.0008) when compared to patients with OSA. Among the clinical determinants of OHS, neither BMI nor AHI showed associations with any postoperative outcomes in univariable or multivariable regression.

Conclusions:  Better emphasis is needed on preoperative recognition of hypercapnia among patients with OSA or overlap syndrome undergoing elective NCS.

original research 
Christopher J. Ryerson; Darragh O’Connor; James V. Dunne; Fran Schooley; Cameron J. Hague; Darra Murphy; Jonathon Leipsic; Pearce G. Wilcox
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Background:  Mortality risk prediction tools have been developed in idiopathic pulmonary fibrosis, however it is unknown whether these models accurately estimate mortality in systemic sclerosis-associated interstitial lung disease (SSc-ILD).

Methods:  Four baseline risk prediction models were calculated in patients recruited from a specialized SSc-ILD clinic, including the Composite Physiologic Index (CPI), the ILD-GAP Index, the du Bois index, and the modified du Bois index. Each baseline model was assessed using logistic regression analysis with 1-year mortality as the outcome variable. Discrimination was quantified using the area under the receiver operating characteristic (AUROC) curve. Calibration was assessed using the goodness of fit test. The incremental prognostic ability of additional predictor variables was determined by adding prespecified variables to each baseline model.

Results:  The 156 patients with SSc-ILD completed 1294 pulmonary function tests, 725 6-minute walk tests, and 637 echocardiograms. Median survival was 15.0 years from the time of SSc-ILD diagnosis. All baseline models were significant predictors of 1-year mortality in SSc-ILD. The modified du Bois index had an AUROC curve of 0.84, compared to 0.77 to 0.81 in the other models. Calibration was acceptable for the modified du Bois index, but was poor for the other models. All baseline models include forced vital capacity, and 6-minute walk distance was identified as an additional independent predictor of 1-year mortality.

Conclusion:  The modified du Bois index has good discrimination and calibration for the prediction of 1-year mortality in SSc-ILD. FVC and 6-minute walk distance are important independent predictors of 1-year mortality in SSc-ILD.

original research 
David J. Blackley, DrPH; A. Scott Laney, PhD; Cara N. Halldin, PhD; Robert A. Cohen, MD
Topics: , , ,

Background  A large body of evidence demonstrates dose-response relationships of cumulative coal mine dust exposure with lung function impairment and with small opacity profusion. However, medical literature generally holds that simple coal workers’ pneumoconiosis (CWP) is not associated with lung function impairment. This study examines the relationship between small opacity profusion and lung function in U.S. underground coal miners with simple CWP.

Methods  Miners were examined during 2005–2013 as part of the Enhanced Coal Workers’ Health Surveillance Program. Work histories were obtained, and chest radiographs and spirometry were administered. For those with multiple Program encounters, the most recent visit was used. Lung parenchymal abnormalities consistent with CWP were classified according to International Labour Organization guidelines, and reference values for FEV1 and FVC were calculated using reference equations derived from the 3rd National Health and Nutrition Examination Survey. Differences in lung function were evaluated by opacity profusion, and regression models were fit to characterize associations between profusion and lung function.

Results  A total of 8,230 miners were eligible for analysis; 269 had category 1 or 2 simple CWP. Decrements in FEV1 percent predicted were nearly consistent across profusion subcategories. Clear decrements in FVC percent predicted and FEV1/FVC were also observed, although these were less consistent. Controlling for smoking status, BMI, and mining tenure, each one-unit subcategory increase in profusion was associated with decreases of 1.5% (95% CI 1.0% to 1.9%), 1.0% (95% CI 0.6% to 1.3%), and 0.6% (95% CI 0.4% to 0.8%) in FEV1 percent predicted, FVC percent predicted, and FEV1/FVC, respectively.

Conclusions  We observed progressively lower lung function across the range of small opacity profusion. These findings address a longstanding question in occupational medicine, and point to the importance of medical surveillance and respiratory disease prevention in this workforce.

original research 
Robert H. Brown, MD; Robert A. Wise, MD; Gregory Kirk, MD; M. Bradley Drummond, MD; Wayne Mitzner, PhD
Topics: ,

Background:  With body growth from childhood, the lungs can enlarge by either increasing the volume of air in the periphery (as would occur with inspiration) or by increasing the number of peripheral acinar units. In the former case the lung tissue density would decrease with inflation, while in the latter case, the lung density would be relatively constant as the lung grows. To address this fundamental structural question, we measured the CT density in human subjects of widely varying size at two different lung volumes.

Methods:  Five-hundred and one subjects were enrolled in the study. They underwent a chest CT at full inspiration, and another scan at end-expiration. Spirometry, body-plethysmography, and DLco were also measured.

Results:  There was a strong correlation between the size of the lungs measured at full inspiration on CT and the mean lung density (r=-.72, p=0.001). People with larger lungs had significantly lower mean lung density. These density changes among different subjects overlapped the density changes within subjects at different lung volumes.

Conclusion:  Lung structure in subjects with larger lungs is different from that in subjects with smaller lungs. Tissue volume does not increase in proportion to lung size, as would be required if bigger lungs just had more alveoli. These observations suggest that growth of the lung into adulthood is not accompanied by new alveoli, but rather by enlargement of existing structures. The presence of bigger air spaces in larger lungs could impact the occurrence and pathogenesis of spontaneous pneumothorax or COPD.

original research 
Matthew A. Rank, MD; Ryan Johnson, MBA, MS; Megan Branda, MS; Jeph Herrin, PhD; Holly van Houten; Michael R. Gionfriddo, PharmD; Nilay D. Shah, PhD

Background:  Long term outcomes after stepping down asthma medications are not well described.

Methods:  This study was a retrospective time-to-event analysis of individuals diagnosed with asthma who stepped down their asthma controller medications using a US claims database spanning 2000-2012. Four-month intervals were established and a step down event was defined by a ≥50% decrease in days-supplied of controller medications from one interval to the next; this definition is inclusive of step down that occurred without healthcare provider guidance or as a consequence of a medication adherence lapse. Asthma stability in the period prior to step down was defined by not having an asthma exacerbation (inpatient visit, emergency department visit, or dispensing of a systemic corticosteroid linked to an asthma visit) and having < 2 rescue inhaler claims in a 4-month period. The primary outcome in the period following step down was time to first asthma exacerbation.

Results:  Thirty-two percent of the 26,292 included individuals had an asthma exacerbation in the 24-month period following step down of asthma controller medication, though only 7% had an emergency department visit or hospitalization for asthma. The length of asthma stability prior to stepping down asthma medication was strongly associated with the risk of an asthma exacerbation in the subsequent 24-month period: < 4 months stability -44%, 4-7 months-34%, 8-11 months-30%, and ≥ 12 months-21%, p<.001.

Conclusion:  In a large, claims-based, real-world study setting, 32% of individuals have an asthma exacerbation in the 2 years following a step down event.

original research 
Hiroshi Sekiguchi, MD; Louis A. Schenck; Ryohei Horie, MD; Jun Suzuki, MD; Edwin H. Lee, MD; Brendan P. McMenomy, MD; Tien-En Chen, MD; Alexander Lekah, MD; Sunil V. Mankad, MD; Ognjen Gajic, MD
Topics: , , , ,

Background:  Pathogenic causes of acute hypoxic respiratory failure (AHRF) can be difficult to identify at early clinical presentation. We evaluated the diagnostic utility of combined cardiac and thoracic critical care ultrasonography (CCUS).

Methods:  Adult patients in the intensive care unit (ICU) were prospectively enrolled from January through September 2010 when the ratio of Pao2 to fraction of inspired oxygen (Fio2) was less than 300 on arterial blood gas (ABG) within 6 hours of a new hypoxic event or ICU admission. Focused cardiac and thoracic CCUS was conducted within 6 hours of ABG testing. Causes of AHRF were categorized into cardiogenic pulmonary edema (CPE), acute respiratory distress syndrome (ARDS), and other, miscellaneous causes after reviewing the hospitalization course in electronic medical records.

Results:  Enrollment involved 134 patients (median [interquartile range] Pao2/Fio2 ratio, 191 [122-253]). Fifty-nine patients (44%) received a CPE diagnosis; 42 (31%), ARDS; and 33 (25%), miscellaneous cause. Analysis on CCUS findings showed that a low B-line ratio (proportion of chest zones with positive B-lines of all zones examined) was predictive for miscellaneous cause vs CPE or ARDS. Area under the receiver operator characteristic curve (AUC) was 0.82 (95% CI, 0.75-0.88). For further differentiation of CPE from ARDS, left pleural effusion (>20 mm), moderately or severely decreased left ventricular function, and a large minimal inferior vena cava diameter (>23 mm) were predictive for CPE. AUC was 0.79 (95% CI, 0.70-0.87).

Conclusions:  Combined cardiac and thoracic CCUS assists in early bedside differential diagnosis of ARDS, CPE, and other causes of AHRF.

ahead of the curve  FREE TO VIEW
Jason R. Biehl, MD; Ellen L. Burnham, MD, MSc
Topics: , ,

Recent legislative successes allowing expanded access to recreational and medicinal cannabis have been associated with its increased use by the public, despite continued debates regarding its safety among the medical and scientific community. Despite legislative changes, cannabis is most commonly used by smoking, although alternatives to inhalation have also emerged. Moreover, the composition of commercially available cannabis has dramatically changed in recent years. Therefore, developing sound scientific information regarding its impact on lung health is imperative, particularly since published data conducted prior to widespread legalization are conflicting and inconclusive. In this Ahead of the Curve, we delineate major observations of recent epidemiologic investigations examining cannabis use and the potential associated development of airways disease and lung cancer to highlight gaps in pulmonary knowledge. Additionally, we will review major histopathologic alterations related to smoked cannabis, and define specific areas in animal models and human clinical translational investigations that could benefit from additional development. Given its ongoing classification as a schedule I medication, federal funding to support investigations of modern cannabis use in terms of medicinal efficacy and safety profile on lung health have been elusive. It is clear, however, that the effects of inhaled cannabis on lung health remain uncertain, and given increasing use patterns, worthy of further investigation.

contemporary reviews in sleep medicine 
Chitra Lal, MD, FCCP, FAASM; Boris I. Medarov, MD; Marc A. Judson, MD
Topics: ,

Sleep-Disordered Breathing (SDB) has a high prevalence in sarcoidosis. The high prevalence may be the result of increased upper airway resistance from sarcoidosis of the upper respiratory tract (SURT), corticosteroid-induced obesity, and parenchymal lung involvement from sarcoidosis. Obstructive sleep apnea (OSA) is a form of SDB that is particularly common in sarcoidosis patients.

  Sarcoidosis and SDB share many similar symptoms and clinical findings, including fatigue, gas exchange abnormalities, and pulmonary hypertension (PH). Sarcoidosis associated fatigue is a common entity for which stimulants may be beneficial. Sarcoidosis associated fatigue is a diagnosis of exclusion that requires an evaluation for the possibility of OSA. Hypercapnia is unusual in a sarcoidosis patient without severe pulmonary dysfunction, and in this situation, should prompt evaluation for alternative causes of hypercapnia such as SDB. PH is usually mild when associated with OSA, whereas the severity of sarcoidosis associated PH is related to the severity of sarcoidosis. PH due to OSA usually responds to continuous positive airway pressure, whereas sarcoidosis-associated PH commonly requires the use of vasodilators.

  Management of OSA in sarcoidosis is problematic as corticosteroid treatment of sarcoidosis may worsen OSA. Aggressive efforts should be made to place the patient on the lowest effective dose of corticosteroids, which involves early consideration of corticosteroid sparing agents. Because of the significant morbidity associated with SDB, early recognition and treatment of SDB in sarcoidosis patients may improve their overall quality of life.

original research 
Adriana C. Lunardi, PhD; Denise M. Paisani, PhD; Cibele C.B. Marques da Silva, MSc; Desiderio P. Cano, MSc; Clarice Tanaka, PhD; Celso R.F. Carvalho, PhD
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Lung expansion techniques (LET) are widely used to prevent postoperative pulmonary complications (PPC). However, the effects of each of these techniques on thoracoabdominal mechanics and PPC incidence after abdominal surgery remain unclear.

OBJECTIVE:  To compare the effects of LET on pulmonary volumes, respiratory muscle activation and PPC incidence after major elective upper abdominal surgery.

METHODS:  This randomized controlled trial enrolled 137 patients, who were randomly assigned into 4 groups: control (CG; n=35), flow incentive spirometry (FIS; n=33), deep breathing (DB; n=35) and volume incentive spirometry (VIS; n=34). Each intervention was performed 3 times per day during 5 days. Subsequently, PPC (pneumonia, atelectasis or severe hypoxemia) were analyzed by a blinded assessor until hospital discharge. Lung volumes (optoelectronic plethysmography) and inspiratory muscular activation (surface electromyography) were assessed before and 3 days after surgery. Statistical analysis was performed considering the intention to treat analysis.

RESULTS:  Before surgery, all groups were homogenous for age, gender, BMI, lung function and thoracoabdominal mechanics. After surgery, no difference was observed in the lung volumes and inspiratory muscular activation during the lung expansion technique (p>0.05). The PPC incidence was higher in the DB group (p<0.05). Higher ASA scores and surgery duration were the only predictors of PPC (n=14, 11.2%).

CONCLUSION:  LET do not modify the changes on thoracoabdominal mechanics or prevent PPC after abdominal surgery. The indiscriminate use of LET should not be routinely prescribed to prevent PPC; however, more studies are required to confirm our results and to change the standard practice.

CLINICAL TRIAL REGISTRATION:  URL: www.clinicaltrials.gov. Identifier: NCT01993602.

original research 
Reinier Snetselaar, MSc; Coline H. M. van Moorsel, PhD; Karin M. Kazemier; Joanne J. van der Vis; Pieter Zanen, MD, PhD; Matthijs F. M. van Oosterhout, MD, PhD; Jan C. Grutters, MD, PhD
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Interstitial lung disease (ILD) is a heterogeneous group of rare diseases which primarily affect the pulmonary interstitium. Studies have implicated a role for telomere length maintenance in ILD, particularly in idiopathic interstitial pneumonia (IIP). Here we measure telomere length in a wide spectrum of sporadic and familial cohorts of ILD and compare telomere length between patient cohorts and controls.

  A multiplex quantitative PCR method was used to measure telomere length in 173 healthy subjects and 359 patients with various ILD, including familial interstitial pneumonia (FIP). The FIP cohort was divided in patients carrying telomerase reverse transcriptase (TERT) mutations, surfactant protein- A2 or –C (SFTP) mutations and patients without a proven mutation (FIP-no mutation)

  Telomere length in all ILDs was significantly shorter compared to controls (p range = 0.038 - 2.28x10-27). Furthermore, telomere length in idiopathic pulmonary fibrosis (IPF) patients was significantly shorter than in other IIP (p=0.002), and than in sarcoidosis patients (p=1.35x10-7). Within the FIP cohort, FIP-TERT patients had the shortest telomeres (p=2.28x10-27), and FIP-no mutation had telomere length comparable to IPF patients (p=0.049). Remarkably, telomere length of FIP-SFTP patients was significantly longer than in IPF patients, but similar to that observed in the other sporadic IIP.

  The results show telomere shortening across all ILD diagnoses. The difference in telomere length between FIP-TERT and FIP-SFTP indicates the distinction between acquired and innate telomere shortening. Short telomere length in IPF an FIP-no mutation is indicative of an innate telomere-biology defect, while a stress induced, acquired telomere shortening might be the underlying process for the other ILD diagnoses.

original research 
Juan-juan Fu, MD, PhD; Vanessa M. McDonald, PhD; Katherine J. Baines, PhD; Peter G. Gibson, MBBS, FRACP
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Background:  The innate inflammatory pathways involved in the frequent exacerbator phenotypes of asthma and COPD are not well understood. This study aimed to investigate airway innate immune activation and systemic inflammation as predictors of exacerbations in asthma and COPD.

Methods:  In this prospective cohort study, baseline airway interleukin (IL)-1β, serum C-reactive protein and IL-6 were assessed in 152 participants with stable asthma (n=63) or COPD (n=89), and related to exacerbations over the following 12 months. Clinical characteristics and inflammatory biomarkers were compared between the frequent (≥2 exacerbations in the follow-up) and infrequent exacerbators. The frequent exacerbation phenotype and exacerbation frequency were analyzed with multivariable modeling. The relationships between airway inflammation, systemic inflammation and future exacerbations were examined using path analysis.

Results:  Ninety-four participants experienced a total of 201 exacerbations, and 36.4% had ≥2 exacerbations. Serum IL-6 (P<0.001) and sputum gene expression and protein levels of IL-1β at baseline were higher in the frequent exacerbators with COPD. Significant pathways initiated by previous exacerbations were identified to occur through activation of the IL-1β-systemic inflammatory axis leading to future exacerbations in COPD. Systemic inflammation was also associated with increased exacerbation risk in asthma.

Conclusion:  Airway IL-1β and systemic inflammation are associated with frequent exacerbations and may mediate a vicious cycle between previous and future exacerbations in COPD. Treatment strategies aimed at attenuating these inflammatory pathways to reduce COPD exacerbations deserve further investigation.

original research 
Bernd Lamprecht; Joan B. Soriano; Michael Studnicka; Bernhard Kaiser; Lowie Vanfleteren; Louisa Gnatiuc; Peter Burney; Marc Miravitlles; Francisco García-Rio; Kaveh Akbari; Julio Ancochea; Ana M. Menezes; Rogelio Perez-Padilla; Maria Montes de Oca; Carlos A. Torres-Duque; Andres Caballero; Mauricio González-García; Sonia Buist; for the BOLD Collaborative Research Group, the EPI-SCAN Team, the PLATINO Team, and the PREPOCOL Study Group

Background  COPD is a frequent condition ranking within the top three causes of mortality in the Global Burden of Disease, yet it remains largely underdiagnosed. We assessed the underdiagnosis of COPD and its determinants in national and international surveys of general populations.

Methods  We analyzed representative samples of adults aged ≥40 years randomly selected from well-defined administrative areas worldwide (44 sites from 27 countries). Post-BD FEV1/FVC<LLN was used to define chronic airflow limitation consistent with COPD. Undiagnosed COPD was considered when participants had post-BD FEV1/FVC<LLN but were not previously diagnosed with COPD.

Results  Among 30,874 participants with a mean age of 56 yrs, 55.8% were female, and 22.9% were current smokers. Population prevalence of (spirometrically defined) COPD ranged from 3.6% in Barranquilla, Colombia to 19.0% in Cape Town, SA. Only 26.4% reported a previous lung function test, and only 5.0% reported a previous diagnosis of COPD, while 9.7% had post-BD FEV1/FVC<LLN. Overall, 81.4% of (spirometrically defined) COPD cases were undiagnosed with the highest rate in Ile-Ife, Nigeria (98.3%) and the lowest rate in Lexington, US (50.0%). In multivariate analysis, a greater probability of being underdiagnosed with COPD was associated with male gender, younger age, never and current smoking, lower education, no previous spirometry and less severe airflow limitation.

Conclusion  Even with substantial heterogeneity in COPD prevalence, COPD underdiagnosis is universally high. Since effective management strategies are available for COPD, spirometry can help to diagnose COPD at a stage when treatment will lead to better outcomes and improved quality of life.

original research 
Vanessa Ieto, PhD; Fabiane Kayamori; Maria I. Montes, MD; Raquel P. Hirata, MS; Marcelo G. Gregório, MD, PhD; Adriano M. Alencar, PhD; Luciano F. Drager, MD, PhD; Pedro R. Genta, MD, PhD; Geraldo Lorenzi-Filho, MD, PhD
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Background:  Snoring is extremely common in the general population and may indicate obstructive sleep apnea (OSA). However, snoring is not objectively measured during polysomnography, and no standard treatment is available for primary snoring or when snoring is associated with mild forms of OSA. This study determined the effects of oropharyngeal exercises on snoring in minimally symptomatic patients with a primary complaint of snoring and diagnosis of primary snoring or mild-to-moderate OSA.

Methods:  Patients were randomized for 3 months of treatment with nasal dilator strips plus respiratory exercises (Control) or daily oropharyngeal exercises (Therapy). Patients were evaluated at study entry and end by sleep questionnaires (Epworth, Pittsburgh) and full polysomnography with objective measurements of snoring.

Results:  We studied 39 patients (age: 46±13 years, body mass index: 28.2±3.1 kg/m2, apnea hypopnea index (AHI): 15.3±9.3 events/hour, Epworth: 9.2±4.9, Pittsburgh: 6.4±3.3). Control (n=20) and Therapy (n=19) groups were similar at study entry. One patient from each group dropped out. Intention-to-treat analysis was used. No significant changes occurred in the Control group. In contrast, patients randomized to Therapy experienced a significant decrease in the Snore Index (snores > 36dB /h): 99.5 [49.6-221.3] vs. 48.2 [25.5-219.2], P = .017 and Total Snore Index (total power of snore/h): 60.4 [21.8-220.6] vs. 31.0 [10.1-146.5], P = .033.

Conclusions:  Oropharyngeal exercises are effective in reducing objectively measured snoring and are a possible treatment for a large population suffering from snoring.

  Clinical trial registered with www.clinicaltrials.gov (NCT01636856).

original research 
Shahrokh Javaheri, M.D.; David Winslow; Pamela McCullough; Paul Wylie; Meir H. Kryger
Topics: ,

Background  Central sleep apnea (CSA), in association with obstructive disordered breathing, occurs in patients using opioids chronically and those with congestive heart failure. In these patients treatment with continuous positive airway pressure (CPAP) frequently fails. The current Adaptive Servo-Ventilation (ASV) devices are promising for the treatment of complex sleep disordered breathing. These devices use algorithms to automatically titrate expiratory and inspiratory pressures. We hypothesized that an ASV device operating automatically would significantly reduce the frequency of breathing events in patients with mixed sleep apnea during polysomnography and with 3 months of treatment.

Design  Prospective, multicenter, observational trial.

Methods  Patients completed 3 nights of attended polysomnography, scored at an independent center. Twenty-seven patients with an apnea hypopnea index (AHI) ≥ 15 and a central apnea index (CAI) ≥ 5 per hour underwent automated ASV titration without technician intervention. 26 patients (96%) used ASV at home for 3 months.

Results  Patients had an AHI of (mean ± SD) 55 ± 24 and CAI of 23 ± 18 at baseline. Overnight, ASV titration improved AHI, CAI, obstructive apnea and arousal index significantly. Patients reported better sleep quality on ASV than CPAP. Over 3 months, ASV remained effective (Median AHI 11 versus 4 during PSG). Mean adherence was 4.2 hours per night. Epworth Sleepiness Scale decreased from 12.8 to 7.8 (p=0.001).

Conclusions  The ASV device treated complex breathing disorders using automated algorithms. Compared to CPAP, patients reported improved sleep quality. Home use of ASV remained effective with acceptable adherence and improvements in daytime sleepiness.

  This trial was registered with Clinical-Trials.gov (NCT01199042)

original research 
N. Omote, MD; H. Taniguchi, MD, PhD; Y. Kondoh, MD, PhD; N. Watanabe, MD; K. Sakamoto, MD, PhD; T. Kimura, MD, PhD; K. Kataoka, MD, PhD; T. Johkoh, MD, PhD; K. Fujimoto, MD, PhD; J. Fukuoka, MD, PhD; K. Otani, MD; O. Nishiyama, MD, PhD; Y. Hasegawa, MD, PhD
Topics: , ,

Background:  Lung-dominant connective tissue disease (LD-CTD) is a disease concept for interstitial pneumonia; however, it has not been robustly validated. This study was conducted to elucidate the clinical, radiologic and histologic features of LD-CTD.

Methods:  We retrospectively reviewed 44 consecutive patients with serologically defined LD-CTD who underwent surgical lung biopsy. Patients were identified as having LD-CTD if they had specific autoantibodies but did not meet the criteria for CTD. We conducted a multidisciplinary diagnosis and evaluated major histologic pattern according to the current idiopathic interstitial pneumonias (IIPs) classification of 2013. Characteristic histologic features for LD-CTD (e.g. prominent plasmacytic infiltration, lymphoid aggregates with germinal centers), high-resolution computed tomography (HRCT) patterns and prognosis were also assessed.

Results:  The major histologic patterns were usual interstitial pneumonia (UIP) in 25 patients, and non-specific interstitial pneumonia (NSIP) in 13. Two or more characteristic histologic features for LD-CTD were observed in 15 histologic UIP (h-UIP) and 11 histologic NSIP (h-NSIP) patients. Fifteen (60%) h-UIP patients showed an inconsistent UIP pattern on HRCT. After multidisciplinary discussion (MDD), 18 h-UIP patients were labeled unclassifiable IIP. The annual change in percent predicted forced vital capacity improved significantly in h-NSIP patients (p=0.002), who also had better survival than those with h-UIP patients (p=0.031). In contrast, survival was not associated with HRCT pattern (p=0.79).

Conclusions:  The major histologic patterns in LD-CTD were UIP followed by NSIP. Two-thirds of patients had characteristic histologic features for LD-CTD. A majority of h-UIP patients were considered to be unclassifiable IIP based on MDD. Patients with h-UIP had worse survival than those with h-NSIP.

original research 
Mei Jiang, Ph.D.; Li-yue Liao, M.D.; Xiao-qing Liu, M.D.; Wei-qun He, M.D.; Wei-jie Guan, Ph.D.; Hao Chen, M.D.; Yi-min Li, M.D.
Topics: , , , ,

Background:  There has been a significant increase in the publication of clinical practice guidelines (CPGs) for respiratory diseases in China. However, little is known about the quality and potential impacts of these CPGs.

Objective:  Our objective was to critically evaluate the quality of Chinese CPGs for respiratory diseases that were published in peer-reviewed medical journals.

Methods:  A systematic search of scientific literature published between 1979 and 2013 was undertaken to identify and select CPGs that were related to respiratory diseases. Four Chinese databases (CBM, WANFANG, VIP and CNKI) were used. The quality of eligible guidelines was independently assessed by four reviewers, using the Appraisal of Guidelines for Research and Evaluation (AGREE) II Instrument. The overall agreement among reviewers was evaluated using an intra-class correlation coefficient (ICC).

Results:  A total of 109 guidelines published in 27 medical journals from 1979 to 2013 were evaluated. The overall agreement among reviewers was considered good (ICC: 0.838; 95% CI: 0.812 to 0.862). The scores of the six AGREE domains were low: 57.3% for scope and purpose (range: 4.2 to 80.5%), 23.8% for stakeholder involvement (range: 2.8 to 54.2%), 7.7% for rigor of development (range: 0 to 27.1%), 59.8% for clarity and presentation (range: 22.2 to 80.6%), 10.9% for applicability (range: 0 to 22.9%), and 0.6% for editorial independence (range: 0 to 16.7%). Scores for all guidelines were below 60%, and only 3 guidelines (2.8%) were recommended for clinical practice with modifications.

Conclusions:  The quality of the guidelines was low, and stakeholder involvement, rigor of development, applicability and editorial independence should be considered in the future development of clinical practice guidelines for respiratory diseases in China.

Arthur F. Gelb, MD, FCCP; Alfred Yamamoto, MD; Eric K. Verbeken, MD; Jay A. Nadel, MD
Topics: , , , , , ,

Investigators believe most asthmatics have reversible airflow obstruction with treatment, despite airway remodeling and hyperresponsiveness. There are smoking and non-smoking patients with chronic expiratory airflow obstruction despite treatment, who have features of both asthma and chronic obstructive pulmonary disease. Investigators refer to this conundrum as the Asthma COPD Overlap Syndrome (ACOS). Furthermore, a subset of treated, non-smoking moderate-to-severe asthmatics, have persistent expiratory airflow limitation, despite partial reversibility. It has been assumed to be due to large and especially small airway remodeling. Alternatively, we and others have described reversible loss of lung elastic recoil in acute and persistent loss in moderate-to-severe chronic asthmatics who never smoked, and its adverse effect on maximal expiratory airflow. The mechanism(s) responsible for loss of lung elastic recoil and persistent expiratory airflow limitation in chronic non-smoking asthmatics consistent with ACOS remain unknown in the absence of structure-function studies. We recently reported a new pathophysiologic observation in 10 never-smoked, treated asthmatics with persistent expiratory airflow obstruction, despite partial reversibility (Gelb AF et al. Letters to Editor. JACI 2014; 133: 263-5). All 10 asthmatics had a significant decrease in lung elastic recoil, and unsuspected, microscopic mild centrilobular emphysema was noted in all 3 autopsies obtained, but was not easily identified on lung CT. These sentinel pathophysiologic observations need to be confirmed to further unravel the epiphenomenon of ACOS. The proinflammatory and proteolytic mechanism(s) leading to lung tissue breakdown need to be further investigated.

recent advances in chest medicine 
Jessica A. Palakshappa, MD; Nuala J. Meyer, MD, MS
Topics: ,

A central tenet to caring for patients with acute respiratory distress syndrome (ARDS) is to treat the underlying cause, be it sepsis, pneumonia, or removal of an offending toxin. Identifying the risk factor for ARDS has even been proposed as essential to diagnosing ARDS. Not infrequently, however, the precipitant for acute hypoxemic respiratory failure is unclear, and this raises the question of whether a histologic lung diagnosis would benefit the patient. In this review, we consider the historic role of pathology in establishing a diagnosis of ARDS and the published experience of surgical and transbronchial lung biopsy in patients with ARDS. We reflect on which pathologic diagnoses influence treatment, and suggest a patient-centric approach to weigh the risk and benefit of a lung biopsy for critically ill patients who may have ARDS.

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