Respiratory Medicine

The effects of cigarette smoke on airway inflammation in asthma and COPD: Therapeutic implications

Asad Tamimi, Dzelal Serdarevic, Nicola A. Hanania — 2011-12-26

Summary: Asthma and COPD are two chronic inflammatory disorders of the airway characterized by airflow limitation. While many similarities exist between these two diseases, they are pathologically distinct due to the involvement of different inflammatory cells; predominantly neutrophils, CD8 lymphocytes in COPD and eosinophils and CD4 lymphocytes in asthma. Cigarette smoking is associated with accelerated decline of lung function, increased mortality, and worsening of symptoms in both asthma and COPD. Furthermore, exposure to cigarette smoke can alter the inflammatory mechanisms in asthma to become similar to that seen in COPD with increasing CD8 cells and neutrophils and may therefore alter the response to therapy. Cigarette smoke exposure has been associated with a poor response to inhaled corticosteroids which are recommended as first line anti-inflammatory medications in asthma and as an add-on therapy in patients with severe COPD with history of exacerbations. While the main proposed mechanism for this altered response is the reduction of the histone deacetylase 2 (HDAC2) enzyme system, other possible mechanisms include the overexpression of GR-β, activation of p38 MAPK pathway and increased production of inflammatory cytokines such as IL-2, 4, 8, TNF-α and NF-Kß. Few clinical trials suggest that leukotriene modifiers may be an alternative to corticosteroids in smokers with asthma but there are currently no drugs which effectively reduce the progression of inflammation in smokers with COPD. However, several HDAC2 enhancers including low dose theophylline and other potential anti-inflammatory therapies including PDE4 inhibitors and p38 MAPK inhibitors are being evaluated.

Characterisation of asthma that develops during adolescence; findings from the Isle of Wight Birth Cohort

2012-01-04

Summary: Background: Understanding of adolescent-onset asthma remains limited. We sought to characterise this state and identify associated factors within a longitudinal birth cohort study.Methods: The Isle of Wight Whole Population Birth Cohort was recruited in 1989 (N=1456) and characterised at 1, 2, 4, 10 and 18-years. “Adolescent-onset asthma” was defined as asthma at age 18 without prior history of asthma, “persistent-adolescent asthma” as asthma at both 10 and 18 and “never-asthma” as those without asthma at any assessment.Results: Adolescent-onset asthma accounted for 28.3% of asthma at 18-years and was of similar severity to persistent-adolescent asthma. Adolescent-onset asthmatics showed elevated bronchial hyper-responsiveness (BHR) and atopy at 10 and 18 years. BHR in this group at 10 was intermediate to that of never-asthmatics and persistent-adolescent asthma. By 18 their BHR, bronchodilator reversibility and sputum eosinophilia was greater than never-asthmatics and comparable to persistent-adolescent asthma. At 10, males who later developed adolescent-onset asthma had reduced FEV1 and FEF25–75, while females had normal lung function but then developed impaired FEV1 and FEF25–75 in parallel with adolescent asthma. Factors independently associated with adolescent-onset asthma included atopy at 10 (OR=2.35; 95% CI=1.08–5.09), BHR at 10 (3.42; 1.55–7.59), rhinitis at 10 (2.35; 1.11–5.01) and paracetamol use at 18-years (1.10; 1.01–1.19).Conclusions: Adolescent-onset asthma is associated with significant morbidity. Predisposing factors are atopy, rhinitis and BHR at age 10 while adolescent paracetamol use is also associated with this state. Awareness of potentially modifiable influences may offer avenues for mitigating this disease state.

Adherence rate to beclomethasone dipropionate and the level of asthma control

Nulma S. Jentzsch, Paulo Camargos, Emanuel S.C. Sarinho, Jean Bousquet — 2011-12-22

Summary: There are only a few studies assessing the relationship between adherence rate to ICS, as assessed by electronic monitoring, and the level of asthma control in childhood. The present study was carried out to examine the relationship between adherence to beclomethasone diproprionate (BDP) as well as other factors related to poor asthma control. In this prospective cohort study, 102 steroid naïve randomly selected subjects with persistent asthma, aged 5–14 years were prescribed 500–750 μg daily of BDP-CFC and followed during one year. Adherence to BDP was measured electronically in the 4th, 8th and 12th months of study. The level of asthma control was classified as either controlled or uncontrolled instead of the current three categories recommended by the Global Initiative for Asthma (GINA). Mean adherence rate was higher in patients with controlled asthma during follow-up, but went down from 60.4% in the 4th month to 49.8% in the 12th month (p = 0.038). Conversely, among patients with uncontrolled asthma, the mean adherence rate decreased from 43.8% to 31.2% (p = 0.001). Multivariate analysis showed that the level of asthma control was independently associated to the adherence rate in all follow-up visits (p-values equal or lower than 0.005). The level of asthma control was directly proportional to adherence rate. Our results suggest that a BDP daily dose by 300 μg seems to be enough to attain control over mild and moderate persistent asthma, including exercise induced asthma.

Status asthmaticus in the medical intensive care unit: A 30-year experience

2011-12-22

Summary: Objectives: To investigate the characteristics, trends in management (permissive hypercapnia; mechanical ventilation (MV); neuromuscular blockade) and their impact on complications and outcomes in Status Asthmaticus (SA).Methods: We performed a retrospective observational study of subjects admitted with SA to a single multidisciplinary MICU over a 30-year period. All laboratory, radiologic, respiratory care, physician notes and orders were extracted from an electronic medical record (EMR) maintained during the entire duration of the study.Results: Two hundred and twenty-seven subjects were admitted with 280 episodes of SA. While subjects reflected our regional population (52% Hispanic), African Americans were over-represented (22%) and Caucasians under-represented (21%). Thirty-eight percent reported childhood asthma, 27% were steroid dependent (10% in the last 10 years), and 18% had a recent steroid taper. One hundred and thirty-nine (61.2%) required intubation. The duration of hospitalization was similar between mechanically ventilated and non-ventilated subjects (5.8±4.41 vs. 6.8±7.22 days; p=0.07). The overall complication rate remained low irrespective of the use of permissive hypercapnia or mode of mechanical ventilation (overall mortality 0.4%; pneumothorax 2.5%; pneumonia 2.9%). The frequency of SA declined significantly in the last 10 years of the study (12.4 vs. 3.2 cases/year).Conclusions: Despite the frequent use of mechanical ventilation, mortality/complication rates remained extremely low. MV did not significantly increase the duration of hospitalization. At our institution, the frequency of SA significantly decreased despite an increase in emergency room visits for asthma.

The role of SPINK5 in asthma related physiological events in the airway epithelium

Esra Birben, Cansın Sackesen, Nihan Turgutoğlu, Ömer Kalayci — 2011-12-02

Summary: Background: Genetic studies have shown that variants in SPINK5 may be associated with atopic diseases and asthma. However, the functional role of SPINK5 protein in asthma has not been elucidated.Objectives: To determine the effects of SPINK5 on asthma related physiological events such as apoptosis, mucus and cytokine production by epithelial cells.Methods: A549 cells were transfected with SPINK5 expression vector and stimulated with increasing doses of hydrogen peroxide and neutrophil elastase (NE) for measurement of cell viability or apoptosis and analysis of mucus production. Cell viability was measured by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5- diphenyl-tetrazolium bromide) assay and apoptosis by Annexin V/PI staining. Levels of IL-4, IL-6, IL-8, IL-12, IL-13, IFNγ, IL-1β and RANTES were determined by ELISA in cell culture supernatants. Mucus production was determined by RT-PCR of the MUC5AC gene and PAS staining in NE treated cells.Results: Epithelial cells transfected with SPINK5 expression vector produced more IL-6, IL-8 and RANTES compared to non-transfected cells (p < 0.001, p = 0.003, p < 0.001, respectively). Even though cells transfected with SPINK5 vector displayed significantly higher cell death, we have not observed any clear effect of SPINK5 on apoptosis. PAS staining showed that SPINK5 slightly decreased the mucin production induced by neutrophil elastase in A549 cells. However, SPINK5 had no effect on MUC5AC transcription.Conclusion: SPINK5 is an important molecule in asthma. Its role extends beyond its well known protease inhibitor properties.

Outcomes of Pseudomonas eradication therapy in patients with non-cystic fibrosis bronchiectasis

2011-12-28

Summary: Pseudomonas aeruginosa infection is associated with poorer outcomes in non-cystic fibrosis bronchiectasis. It is unknown whether early eradication improves outcomes. This retrospective study assessed clinical and microbiological outcomes of eradication therapy following initial Pseudomonas infection.All patients undergoing Pseudomonas eradication therapy from 2004 to 2010 were identified retrospectively and assessed for microbiological eradication, exacerbation frequency, hospital admissions, clinical symptoms and lung function.30 patients were identified with median follow-up time 26.4 months. Eradication therapy involved intravenous antibiotics (n = 12), intravenous antibiotics followed by oral ciprofloxacin (n = 13) or ciprofloxacin alone (n = 5), combined with 3 months of nebulised colistin. Pseudomonas was initially eradicated from sputum in 24 patients (80.0%). 13/24 patients remained Pseudomonas-free and 11/24 were subsequently reinfected (median time 6.2 months). Exacerbation frequency was significantly reduced from 3.93 per year pre-eradication and 2.09 post-eradication (p = 0.002). Admission rates were similar, at 0.39 per year pre-eradication and 0.29 post-eradication (p = NS). 20/30 patients reported initial clinical improvement, whilst at one-year follow up, 19/21 had further improved or remained stable. Lung function was unchanged.This study demonstrates that Pseudomonas can be eradicated from a high proportion of patients, which may lead to prolonged clearance and reduced exacerbation rates. This important outcome requires confirmation in a prospective study.

The prevalence of undiagnosed renal failure in a cohort of COPD patients in western Norway

Bjarte Gjerde, Per S. Bakke, Thor Ueland, Jon A. Hardie, Tomas M.L. Eagan — 2011-11-30

Summary: Patients with COPD are at risk for other comorbid diseases, like heart failure, coronary heart disease, and depression. However, little is known about COPD phenotypes and prevalence of sub-clinical renal failure.433 COPD patients and 233 subjects without COPD, from Western Norway, age 40–75, GOLD stage II–IV, were examined in 2006/07 upon entry to the Bergen COPD Cohort Study. Plasma creatinine was measured in 422 of the COPD patients. The Glomerular Flow Rate (GFR) was determined with the Cockcroft Gault formula, and having a GFR < 60 was defined as renal failure. Examined explanatory factors were sex, age, smoking habits, GOLD stage, hypoxemia, exacerbation history, cachexia, use of daily inhaled steroids, Charlson comorbidity score, use of ACE inhibitors and/or ARBs, and the inflammatory plasma markers C-reactive protein (CRP), soluble tumor necrosis factor receptor 1 (sTNF-R1) and neutrophil gelatinase associated lipocalin (NGAL). Associations between explanatory variables and renal failure were examined by a logistic regression analysis.The prevalence of having GFR < 60 was 9.6% in female COPD patients and 5.1% in male COPD patients (p = 0.08). In multivariable analysis, female sex, higher age, cachexia, and the inflammatory markers sTNF-R1 and NGAL were all independently associated with a higher risk for renal failure, whereas use of inhaled steroids, Charlson score, GOLD stage, respiratory failure, and exacerbation frequency were not.Undiagnosed renal failure is a concern particularly in elderly COPD patients and COPD patients with cachexia.

Impairment of quality of life in women with chronic obstructive pulmonary disease

Karlos Naberan, Ángel Azpeitia, Jordi Cantoni, Marc Miravitlles — 2011-10-24

Summary: Background: There is ample evidence of the differences between genders in chronic obstructive pulmonary disease (COPD). The purpose of this study was to identify the factors that contribute to these differences.Methods: This was a multi-center, cross-sectional observational study including 4574 patients of 40 years of age and older who attended primary care and pulmonary clinics. Data were collected on COPD characteristics, comorbidities, quality of life as assessed by both the EuroQoL 5D questionnaire (EQ-5D) and the Airways Questionnaire 20 (AQ20), and prevalence of anxiety and depression. Data collected were compared between males and females.Results: Mean age was 67 years and 740 patients (16.7%) were female. Women were significantly younger, had better pulmonary function, and smoked less; however, they showed poorer quality of life (EQ-5D: 0.6 [SD = 0.3] versus 0.7 [0.3]; p < 0.001; and AQ20: 10.4 [SD = 4.6] versus 9.2 [SD = 4.5]; p < 0.001) and a higher rate of anxiety (34.5% versus 20.6%; p < 0.001) and depression (31.7% versus 22.1%; p < 0.001). In a multivariate analysis, female gender was significantly associated to poorer quality of life (AQ20) but not to a higher rate of dyspnea.Conclusion: Women with COPD are younger and have lower rates of impaired lung function; however, they show poorer quality of life and more frequent COPD-associated anxiety and depression.

Barriers to adherence to COPD guidelines among primary care providers

2011-10-14

Summary: Background: Despite efforts to disseminate guidelines for managing chronic obstructive pulmonary disease (COPD), adherence to COPD guidelines remains suboptimal. Barriers to adhering to guidelines remain poorly understood.Methods: Clinicians from two general medicine practices in New York City were surveyed to identify barriers to implementing seven recommendations from the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. Barriers assessed included unfamiliarity, disagreement, low perceived benefit, low self-efficacy, and time constraints. Exact conditional regression was used to identify barriers independently associated with non-adherence.Results: The survey was completed by 154 clinicians. Adherence was lowest to referring patients with a forced expiratory volume in 1 s (FEV1) <80% predicted to pulmonary rehabilitation (5%); using FEV1 to guide management (12%); and ordering pulmonary function tests (PFTs) in smokers (17%). Adherence was intermediate to prescribing inhaled corticosteroids when FEV1 <50% predicted (41%) and long-acting bronchodilators when FEV1 <80% predicted (54%). Adherence was highest for influenza vaccination (90%) and smoking cessation counseling (91%). In unadjusted analyses, low familiarity with the guidelines, low self-efficacy, and time constraints were significantly associated with non-adherence to ≥2 recommendations. In adjusted analyses, low self-efficacy was associated with less adherence to prescribing inhaled corticosteroids (OR: 0.28; 95% CI: 0.10, 0.74) and time constraints were associated with less adherence to ordering PFTs in smokers (OR: 0.31; 95% CI: 0.08, 0.99).Conclusions: Poor familiarity with recommendations, low self-efficacy, and time constraints are important barriers to adherence to COPD guidelines. This information can be used to develop tailored interventions to improve guideline adherence.

Comparison of tiotropium plus fluticasone propionate/salmeterol with tiotropium in COPD: A randomized controlled study

2011-10-05

Summary: Background: The combination of tiotropium and fluticasone propionate/salmeterol (FSC) is commonly used to treat chronic obstructive pulmonary disease (COPD), but no study had evaluated the effectiveness of tiotropium plus FSC with 250 μg of fluticasone propionate. Our aim was to assess whether tiotropium (18 μg once daily) plus FSC (250/50 μg twice daily) provides better clinical outcomes compared to tiotropium monotherapy.Methods: In this 24-week, randomized, open label, multicenter two-arm parallel study, 479 patients received tiotropium plus FSC (n = 237) or tiotropium alone (n = 242).Results: After 24 weeks of treatment, the triple-inhaled treatment group had a significant improvement in pre-bronchodilator FEV1 (L) compared to the tiotropium-only group (0.090 L vs. 0.038 L; P = 0.005). Regarding health-related quality of life, the mean change in total score on the St. George’s Respiratory Questionnaire for COPD patients (SGRQ-C) was −6.6 points in the tiotropium plus FSC group, but −1.5 points in the tiotropium-only group (P = 0.001). In the subgroup of GOLD stage II patients with COPD, treatment with tiotropium plus FSC also improved FEV1 compared to tiotropium alone (0.088 L vs. 0.030 L; P = 0.011) and improved the total SGRQ-C score than tiotropium alone (−4.5 points vs. −1.0 points, respectively). This triple-inhaled treatment approach did not induce more adverse events, such as pneumonia.Conclusion: Over the course of 24 weeks, FSC (250/50 μg twice daily) added to tiotropium provided greater improvement in lung function and quality of life in patients with COPD (FEV1 ≤ 65%) than tiotropium alone.

Development of the i-BODE: Validation of the incremental shuttle walking test within the BODE index

2011-10-05

Summary: Background: The BODE index has been shown to predict mortality in COPD. The index includes the 6 min walking test as the measure of exercise capacity. The incremental shuttle walking test (ISWT) is an alternative measure of exercise capacity which can be used to prescribe exercise and has been found to correlate well with peak VO2. The objective of the study was to evaluate the incorporation of the ISWT within the BODE index (named the i-BODE) to predict mortality in COPD.Methods: Data was analysed from 633 patients with COPD attending pulmonary rehabilitation over an 11 year period, and mortality determined a minimum of one year on from initial assessment. An i-BODE score was calculated using ISWT(m) then Cox regression analysis evaluated the capacity of the index to predict risk of death.Results: BMI, ISWT (m), MRC dyspnoea score, pack years and age were all significantly associated with mortality. Cox regression revealed the i-BODE index was an independent and significant predictor of mortality (hazard ratio 1.27 (CI 1.17–1.35), p < 0.001) and Kaplan Meier survival analysis showed each quartile increase in severity in i-BODE score was significantly associated with increased mortality (p < 0.001 by log rank test).Conclusion: We have found the i-BODE index to be an independent predictor of mortality in COPD, even when other strong predictors such as age and pack years are adjusted for. We conclude that the ISWT can be successfully substituted for the 6MWT as an alternative measure of exercise capacity within the BODE index.

Is chronic obstructive pulmonary disease associated with increased arterial stiffness?

2011-12-05

Summary: Objective: We hypothesize that airflow limitation is associated with increasing arterial stiffness and that having COPD increases a non-invasive measure of arterial stiffness – the aortic augmentation index (AIx) – independently of other CVD risk factors.Methods: This population study is based on 3374 subjects from the Copenhagen City Heart Study; 494 had COPD. We used multiple linear regression analyses to examine the association between COPD and AIx adjusted for CVD risk factors. Furthermore, we analyzed the association between AIx and FEV1, FVC and FEV1/FVC in the entire population.Results: AIx was higher in subjects with COPD than in subjects without: 25.7 vs. 21.0 (p < 0.001) in men and 33.6 vs. 29.4 (p < 0.001) in women. We found no increase in AIx with COPD adjusted for CVD risk factors: difference 0.63 (−0.26 to 1.52, p = 0.16). In sensitivity analyses in subjects younger than 60 years with exclusion of mild COPD from the analyses, COPD was associated with an increase in AIx in men only of 4.1 (0.88–7.22, p = 0.007). AIx had a curvilinear association with FEV1 and FVC but no association with the FEV1/FVC ratio.Conclusion: AIx and COPD are only weakly associated. In the general population, this finding argues against increased arterial stiffness, as measured by AIx, being a complication of COPD.

Effect of cigarette smoking on cough reflex induced by TRPV1 and TRPA1 stimulations

Masashi Kanezaki, Satoru Ebihara, Peijun Gui, Takae Ebihara, Masahiro Kohzuki — 2011-12-30

Summary: Background: Recent studies have shown that neurogenic inflammation induced by cigarette smoke is inhibited by TRPA1 antagonist, but not by TRPV1 antagonist. Since cough reflex sensitivity is known to be modified by smoking status, we investigated the effects of cigarette smoking on TRPA1- and TRPV1-induced cough and urge-to-cough in healthy males.Methods: Twenty-six healthy never-smokers and 30 healthy current smokers were recruited via public postings. Cough reflex thresholds and urge-to-cough were evaluated by inhalation of capsaicin, a TRPV1 agonist, and cinnamaldehyde, a TRPA1 agonist. The cough reflex thresholds were defined as the lowest concentrations of capsaicin and cinnamaldehyde that elicited two or more coughs (C2) and five or more coughs (C5), respectively. The urge-to-cough was evaluated using the modified Borg scale.Results: In capsaicin-induced cough, the cough reflex thresholds, as expressed by C2 and C5, in current smokers were significantly higher than those in never-smokers (p<0.01 and p<0.001, respectively). The urge-to-cough log–log slopes in current smokers were significantly lower than those of never-smokers (p<0.001). There were no significant differences in the thresholds of the urge-to-cough between never-smokers and current smokers. In cinnamaldehyde-induced cough, there were no significant differences in cough reflex thresholds in C2 and C5 between never-smokers and current smokers, nor were there any significant differences in urge-to-cough log–log slope between never-smokers and current smokers. There were no significant differences in the thresholds of the urge-to-cough between never-smokers and current smokers.Conclusion: The study suggests that smoking has a differential effect on cough responses between TRPV1 and TRPA1 stimulations.

The clinical implications of bronchoscopy in hemoptysis patients with no explainable lesions in computed tomography

2011-12-14

Summary: Introduction: Hemoptysis is observed frequently in patients, although chest computed tomography (CT) shows no explainable lesion as the cause of hemoptysis. However, the clinical course of these patients has not been reported fully.Methods: This study included patients who visited Seoul National University Hospital and Seoul National University Bundang Hospital to be treated for hemoptysis from January 2003 through October 2009 and who had no lesion causing hemoptysis in chest CT. We retrospectively analyzed their bronchoscopic and clinical findings.Results: A total of 228 patients were included, and the mean follow-up duration was 781 days. All patients underwent bronchoscopy. The bronchoscopic findings of 191 patients (83.8%) were negative for hemoptysis and showed the possible causes of bleeding in 37 patients (16.2%). Forty-three of the 191 patients with negative bronchoscopic findings had oronasopharyngeal problems or were using anticoagulants. After excluding these 43 patients, hemoptysis recurred in 29 (19.6%) of the remaining patients. Thirteen of the patients whose bronchoscopic findings identified the possible causes of bleeding (35.1%) experienced recurrence. Only one patient (0.4%) was diagnosed with lung cancer by the initial bronchoscopy, and no patient developed malignancy during the follow-up period.Conclusion: The recurrence rate was higher in the patients with positive findings than in the patients with negative findings on bronchoscopy. Although about 20% of patients with negative bronchoscopy findings experienced recurrence, the clinical course of those in whom recurrent bleeding occurred was usually benign.

Sleep desaturation and its relationship to lung function, exercise and quality of life in LAM

2012-01-05

Summary: Background: Lymphangioleiomyomatosis (LAM) is characterised by progressive airway obstruction and hypoxaemia in young women. Although sleep may trigger hypoxaemia in patients with airway obstruction, it has not been previously investigated in patients with LAM.Methods: Consecutive women with lung biopsy proven LAM and absence of hypoxaemia while awake were evaluated with pulmonary function test, echocardiography, 6-min walk test, overnight full polysomnography, and Short Form 36 health-related quality-of-life questionnaire.Results: Twenty-five patients with (mean±SD) age 45±10 years, SpO2 awake 95%±2, forced expiratory volume in the first second (median–interquartile) FEV1(% predicted) 77 (47–90) and carbonic monoxide diffusion capacity, DLCO (%) 55 (34–74) were evaluated. Six-minute walk test distance and minimum SpO2 (median–interquartile) were, respectively, 447m (411–503) and 90% (82–94). Median–interquartile apnoea–hypopnoea index was in the normal range 2 (1–5). Fourteen patients (56%) had nocturnal hypoxaemia (10% total sleep time with SpO2 <90%), and the median sleep time spent with SpO2 <90% was 136 (13–201)min. Sleep time spent with SpO2 <90% correlated with the residual volume/total lung capacity ratio (rs=0.5, p: 0.02), DLCO (rs=−0.7, p: 0.001), FEV1 (rs=−0.6, p: 0.002). Multivariate linear regression model showed that RV/TLC ratio was the most important functional variable related to sleep hypoxaemia.Conclusion: Significant hypoxaemia during sleep is common in LAM patients with normal SpO2 while awake, especially among those with some degree of hyperinflation in lung function tests.

Predictors of benefit following pulmonary rehabilitation for interstitial lung disease

2011-12-19

Summary: Background: Pulmonary rehabilitation improves functional capacity and symptoms in the interstitial lung diseases (ILDs), however there is marked variation in outcomes between individuals. The aim of this study was to establish the impact of the aetiology and severity of ILD on response to pulmonary rehabilitation.Methods: Forty-four subjects with ILD, including 25 with idiopathic pulmonary fibrosis (IPF), underwent eight weeks of pulmonary rehabilitation. Relationships between disease aetiology, markers of disease severity and response to pulmonary rehabilitation were assessed after eight weeks and six months, regardless of program completion.Results: In IPF, greater improvements in 6-minute walk distance (6MWD) immediately following pulmonary rehabilitation were associated with larger forced vital capacity (r = 0.49, p = 0.01), less exercise-induced oxyhaemoglobin desaturation (rS = 0.43, p = 0.04) and lower right ventricular systolic pressure (r = −0.47, p = 0.1). In participants with other ILDs there was no relationship between change in 6MWD and baseline variables. Less exercise-induced oxyhaemoglobin desaturation at baseline independently predicted a larger improvement in 6MWD at six month follow-up. Fewer participants with IPF had clinically important reductions in dyspnoea at six months compared to those with other ILDs (25% vs 56%, p = 0.04). More severe dyspnoea at baseline and diagnosis other than IPF predicted greater improvement in dyspnoea at six months.Conclusions: Patients with IPF attain greater and more sustained benefits from pulmonary rehabilitation when disease is mild, whereas those with other ILDs achieve benefits regardless of disease severity. Early referral to pulmonary rehabilitation should be considered in IPF.

Acute exacerbation of IPF following diagnostic bronchoalveolar lavage procedures

2011-12-05

Summary: Backgrounds: Bronchoalveolar lavage (BAL) is generally regarded as a safe diagnostic procedure. However, acute exacerbation after BAL is increasingly recognized as a specific complication for patients with idiopathic pulmonary fibrosis (IPF). So far little is known about the correlation between BAL and acute exacerbation of IPF (AE-IPF).Methods: A cohort of 112 IPF patients at a single institution was analyzed retrospectively. We defined BAL-related AE-IPF as development of AE-IPF within 30 days after the procedure. The incidence rate of AE-IPF per person-month during the post-BAL period was compared with that after the post-BAL period. The relative risk was estimated as the former rate divided by the latter. We also reviewed the previous literature.Results: Four AE-IPF cases occurred during the 201 person-month post-BAL period. The risk of AE-IPF was significantly elevated within 30 days after BAL (rate ratio = 4.12; 95% CI = 1.03–12.2). None of the 111 initial BAL procedures were followed by AE-IPF within a month. In a post hoc analysis, the relative risk of developing AE after second or later BAL procedures was estimated to be considerably higher (rate ratio = 9.10; 95% CI = 2.27–26.98).Twelve cases of BAL-induced AE-IPF were found in our study and in the literature review. Among them, nine showed moderate to severe functional impairment, and eight had either findings of leukocytosis, positive C-reactive protein, or neutrophilia in BAL.Conclusions: These results suggest that IPF patients should be carefully monitored after BAL, especially those with functional impairment or active inflammation.

Adverse pulmonary reactions associated with the use of monoclonal antibodies in cancer patients

2011-12-12

Summary: Background: The incidence and clinical characteristics of adverse pulmonary reactions resulting from anticancer monoclonal antibody (mAbs) therapy have not been well described. We determined the incidence and clinical characteristics of adverse pulmonary reactions in patients treated with anticancer chemotherapy including mAbs.Methods: A retrospective cohort study was performed including patients who were treated with a chemotherapeutic regimen that included rituximab, trastuzumab, cetuximab, or bevacizumab at Seoul National University Hospital between January 1, 2004 and December 31, 2008. Rates of adverse pulmonary reactions classified as non-infectious and infectious complications were compared with those among patients treated with comparable regimens without mAbs.Results: In total, 1078 patients were included (418 for rituximab, 329 for trastuzumab, 122 for cetuximab, 209 for bevacizumab). Adverse pulmonary reactions were identified in 36 patients (3.5%) and the incidence differed among agents: cetuximab (9%), rituximab (5.3%), trastuzumab (0.6%), bevacizumab (0.5%). Infectious pulmonary complications occurred in 28 patients, and eight patients experienced non-infectious pulmonary complications, most commonly interstitial lung disease (6 patients). In a multivariate analysis, low serum albumin level was associated with the development of pulmonary complications. The incidence of overall adverse pulmonary reactions did not differ between the mAbs users and the 1012 patients treated with comparable regimens other than mAbs (3.5% vs. 2.8%, P=0.53).Conclusions: Infectious and non-infectious adverse pulmonary reactions occur in patients with cancer who are administered a regimen including mAbs. Clinicians should be alert for the possibility of pulmonary adverse reactions, particularly among patients with low serum albumin levels.

Guideline adherence and macrolides reduced mortality in outpatients with pneumonia

2011-12-19

Summary: Background: For outpatients with pneumonia, guidelines recommend empiric antibiotics and some suggest macrolides are preferred agents. We hypothesized that both guideline-concordant antibiotics and macrolides would be associated with reduced mortality.Methods: All outpatients with pneumonia assessed at 7 Emergency Departments in Edmonton, Alberta, Canada were enrolled in a population-based registry that included clinical-radiographic data, Pneumonia Severity Index (PSI) and treatments. Guideline-concordant regimens included macrolides and respiratory fluoroquinolones; other regimens were “discordant”. Main outcome was 30-day all-cause mortality.Results: The study included 2973 outpatients; mean age 51 years, 47% female, most had mild pneumonia (73% PSI Class I–II). Over 30-days, 38 (1%) patients died, 228 (8%) were hospitalized, and 253 (9%) reached the endpoint of death or hospitalization. Most (2845 [96%]) patients received guideline-concordant antibiotics. Compared to patients receiving discordant antibiotics, those receiving guideline-concordant antibiotics were less likely to die within 30-days (8 [6%] versus 30 [1%], adjusted OR 0.23, 95% CI 0.09–0.59, p = 0.002). Within the guideline-concordant subgroup, compared to the 947 (33%) patients treated with fluoroquinolones, those receiving macrolides [1847 (64%)] were less likely to die (25 [3%] versus 4 [0.2%], adjusted OR 0.28, 95% CI 0.09–0.86, p = 0.03).Conclusions: In outpatients with pneumonia, treatment with guideline-concordant antibiotics and macrolides were both associated with mortality reduction.

Nocturnal gastroesophageal reflux, lung function and symptoms of obstructive sleep apnea: Results from an epidemiological survey

2011-12-26

Summary: Background: Nocturnal gastroesophageal reflux (nGER) has received increasing interest as a predisposing factor for respiratory diseases and sleep disturbances. The possible role of obstructive sleep apnea (OSA) contributing to nGER is of special interest. The aim of this study was to explore the association between nGER and respiratory diseases, lung function and symptoms of OSA.Methods: Participants in the Burden of Obstructive Lung Disease (BOLD) initiative in Iceland and Sweden, a random sample from the general population of 1325 adults aged 40+ (>70% response rate), were compared by pre- and post-bronchodilator spirometry, answers to questionnaires about OSA and respiratory symptoms, health, and symptoms of GER.Results: Altogether 102 (7.7%) reported nGER and 249 had used medication against GER. The participants were divided into three groups: 1) No nGER (n = 1040), 2) treated GER without nGER (n = 183) and 3) nGER (n = 102). The nGER group had a significantly higher prevalence of respiratory and OSA symptoms than subjects without nGER. The nGER group also had a higher prevalence of COPD (GOLD stage 1+), (25.0% vs. 15.6%) (p = 0.02) and lower FEV1/FVC ratio (95.9% vs. 98.9% of the predicted, p = 0.01). These associations remained significant after adjusting for smoking, weight and other possible confounders. No independent association was found between having treated GER and lung function, respiratory or OSA symptoms.Conclusions: In our cross-sectional epidemiological study, untreated nGER is strongly associated with both respiratory and OSA symptoms as well as airflow obstruction.

Chronic bronchitis in the general population: Influence of age, gender and socio-economic conditions

2011-12-26

Summary: Chronic bronchitis (CB) is an indicator of an increased risk of developing COPD, but its symptoms are often underestimated. Demographic and socio-economic conditions might influence its prevalence, reporting and impact.Data from a large epidemiological survey of the French general population were analyzed to determine the burden of CB, the magnitude of under-diagnosis and the influence of age, gender and socio-economic conditions. Altogether, 9050 participants aged 45 years or more provided complete data.The prevalence of symptoms and diagnosis of CB was 3.5% and 3.4%, respectively. CB was associated with impaired health status and activity and, in women, work loss. Among subjects with symptoms of CB, only 28.6% declared a known diagnosis of respiratory disease. Factors associated with symptoms of CB in multivariate analysis were male gender, active smoking, lower income and occupational category: the highest prevalence was observed in manual workers (5.6%) and self-employed subjects (5.2%). The under-diagnosis of CB was more marked in men and subjects of higher socio-economic categories.These results confirm that CB is markedly under-diagnosed in the general population. Socio-economic conditions influence both its prevalence (higher in low categories) and rate of diagnosis (lower in high categories), which should be considered when elaborating prevention and detection campaigns.