Respiratory Medicine

Airway bacterial colonization: The missing link between COPD and cardiovascular events?

Salvatore Fuschillo, Michele Martucci, Claudio F. Donner, Giovanni Balzano — 2012-04-30

Summary: Background: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide and, according to the World Health Organization, its prevalence will double by 2020. COPD is a chronic inflammatory disease of the lung characterized by poorly reversible airflow limitation and, frequently, by extrapulmonary manifestations. In particular, the cardiovascular manifestations are responsible for high morbidity and mortality.Methods and results: A systematic literature search was performed of studies published in Medline until December 2010, using the key-words: COPD, bacterial colonization, COPD exacerbation, atherosclerosis, systemic inflammation, cardiovascular event and risk factors. In addition to the studies identified in the primary search, reference lists of included articles were analyzed for additional papers related to the topic.The pathogenetic mechanisms underlying atherosclerosis – namely inflammation, oxidative stress and endothelial dysfunction – are in common with COPD. Moreover, they are increased in the presence of COPD, especially in patients who present airway bacterial colonization, increased rate of exacerbations and elevated levels of both airway and systemic inflammation.Conclusion: COPD is associated with an increased burden of atherosclerotic disease. Systemic inflammation and oxidative stress play key roles in this association. COPD patients with airway bacterial colonization, as compared to patients without airway colonization, generally present more frequent exacerbations and higher levels of both airway and systemic inflammation. This COPD subgroup should be considered at particularly increased risk of developing cardiovascular complications and receive more attention concerning diagnosis, treatment, prevention and research.

Mental health among adults with asthma and chronic bronchitis. A population-based study in Spain

2012-04-26

Summary: Objectives: To analyze the conditions of psychological dysfunction and positive mental health in patients with asthma and chronic bronchitis (CB), as compared to healthy individuals, and to identify the factors associated with these mental health indicators.Methods: Cross-sectional study based on data obtained from the European Health Interview Survey for Spain (EHISS, 2009). We identified individuals with asthma and CB using a specific questionnaire. In order to assess mental health, two indicators extracted from questionnaire SF-36 were used: psychological dysfunction and positive mental health status.Results: Out of 19,598 subjects included in the study, 8.3% were classified as asthmatic and 7.4% as CB. Healthy individuals had significantly higher psychological dysfunction scores than those with asthma and CB. The same occurred with positive mental health. The variables independently associated with lower scores out of these variables were gender female, a greater number of chronic diseases and obesity. On the contrary, alcohol consumption and physical exercise were associated with a higher score in the aforementioned variables.Conclusions: Healthy individuals have significantly higher scores in psychological dysfunction and positive mental health than patients with asthma and CB. This suggests that their mental health is much better. The variables related with lower scores out of these variables, and therefore with worse mental health, are: being female, having a greater number of chronic diseases and obesity. On the contrary, alcohol consumption and the practicing of physical exercise are associated with a higher score in the aforementioned variables, thus indicating a greater degree of mental health.

Association between asthma medications and suicidal ideation in adult asthmatics

Helene Favreau, Simon L. Bacon, Maryann Joseph, Manon Labrecque, Kim L. Lavoie — 2012-04-11

Summary: Background: Asthma has been associated with suicidal ideation (SI), though the mechanisms remain poorly understood. Some asthma medications (e.g., theophylline and beta-2 adrenergic agonists) have been shown to provoke feelings of anxiety, fear, and irritability, but their link to SI among asthmatics has not been examined, which was the purpose of the present study.Methods: 664 adult asthma outpatient (39% male, M age = 49 ± 14.3) underwent a sociodemographic, psychiatric, and medical history interview. Patients reported asthma medication use, which was verified by chart review. All patients underwent spirometry and completed questionnaires including the beck depression inventory-II (BDI-II) which includes an item that assesses SI in the past two weeks.Results: 11.5% of patients reported having SI in the past two weeks. After adjusting for age, sex, smoking, asthma severity, and depressive disorders, analyses indicated that theophylline use was associated with an increased likelihood of SI (OR = 2.67, 95% CI = 1.07–6.65). Sensitivity analyses including asthma control levels and benzodiazepine use as additional covariates did not alter this association (respectively: OR = 2.54, 95% CI = 1.04–6.37; OR = 2.71, 95% CI = 1.09–6.78), though adding cohabitation rendered it no longer statistically significant (OR = 2.34, 95% CI = 0.90–6.09). There were no associations between SI and LABA use.Conclusions: Findings suggest that theophylline but not LABA use may be associated with an increased risk of SI among adult asthmatics independent of depressive disorders, asthma control levels, and asthma severity, but not cohabitation, suggesting that cohabitation may be important for SI in this population. Physicians should be cautious when prescribing theophylline or similar agents to asthmatics, and ensure adequate follow-up.

Serologic allergic bronchopulmonary aspergillosis (ABPA-S): Long-term outcomes

2012-03-26

Summary: Background and aim: ABPA is radiologically classified on the presence or absence of central bronchiectasis (CB) as ABPA-CB and serologic ABPA (ABPA-S) respectively. Few studies have described the follow-up of patients with ABPA-S. The aim of this retrospective study was to describe the outcomes of ABPA-S.Methods: Patients were diagnosed as ABPA-S if they met all the following criteria: asthma, immediate cutaneous hyperreactivity to Aspergillus fumigatus antigen, total IgE levels >1000 IU/mL, A. fumigatus specific IgE levels >0.35 kUA/L and normal HRCT of the chest. They were treated with glucocorticoids and followed up with history, physical examination, chest radiograph and total IgE levels every 6 weeks to 3 months. In addition, an annual spirometry and a biennial HRCT chest were performed in all patients.Results: Of the 55 patients with ABPA-S, 41 (17 men, 24 women; mean age, 38.3 years) consented for performance of repeat HRCT scans. The median duration of asthma prior to diagnosis of ABPA was six years. The duration of follow-up ranged from 24 to 77 months with the mean (SD) follow-up duration being 43.7 (10.1) months. There was improvement in FEV1 but not the FVC values during the follow-up period (p values = 0.001 and 0.5 for FEV1 and FVC respectively). There was no development of CB in any patient. Sixteen patients had a relapse during the follow-up period, and six patients were classified as glucocorticoid-dependent ABPA.Conclusions: Although relapses are frequently seen, the long-term outcome of ABPA-S is good with no patient developing CB.

Association of adult-onset asthma with specific cardiovascular conditions

Hwa Mu Lee, Steven T. Truong, Nathan D. Wong — 2012-03-26

Summary: Background: While asthma is known to be associated with cardiovascular disease (CVD), the relation to specific manifestations of CVD has not been previously described. Our objective was to explore the relation of child and adult-onset asthma with specific CVD conditions.Methods: We examined data from 16,943 (projected 178 million) U.S. adults aged 18–90 years old with relevant information on asthma and CVD. The study was a cross-sectional analysis of the National Health and Nutrition Examination Survey 1999–2006. We determined the prevalence of CVD risk factors and likelihood of CVD conditions according to gender and asthma status using multiple logistic regression adjusted for age, gender and other CVD risk factors.Results: The proportions of subjects with child and adult-onset asthma were 4.8% (n=702) and 3.3% (n=534), respectively. Adult-onset asthma was significantly associated with total CVD (OR=2.07, CI=1.2–3.7), but child-onset asthma was not associated with any CVD conditions. Of the four specific CVD endpoints, adult-onset asthma overall was only associated with coronary heart disease (CHD) (OR=2.26, CI=1.2–4.2) in the total population.Conclusions: Our data suggests that CHD is the major cardiovascular condition associated with asthma; a prospective study must be done to confirm a causal relationship.

Downregulation of lung mitochondrial prohibitin in COPD

2012-04-23

Summary: Prohibitins (PHB1 and PHB2) are versatile proteins located at the inner mitochondrial membrane, maintaining normal mitochondrial function and morphology. They interact with the NADH dehydrogenase protein complex, which is essential for oxidoreductase activity within cells. However, their expression in lung epithelium, especially in smokers and patients with inflammatory lung diseases associated with increased oxidative stress, such as COPD, is unknown. Lung tissue specimens from 45 male subjects were studied: 20 COPD patients [age: 65.7 ± 5.8 years, smoking: 84.6 ± 33.6 pack-years, FEV1 (%pred.): 58.7 ± 14.6, FEV1/FVC (%): 63.8 ± 9.4], 15 non-COPD smokers [age: 59.0 ± 12.1 years, smoking: 52.5 ± 20.8 pack-years, FEV1 (%pred.): 85.5 ± 14.2, FEV1/FVC (%): 78.5 ± 4.7] and 10 non-smokers. Quantitative real-time PCR experiments were carried out for PHB1 and PHB2, using β-actin as internal control. Non-COPD smokers exhibited lower PHB1 mRNA levels when compared to non-smokers (0.55 ± 0.06 vs. 0.90 ± 0.06, P = 0.043), while PHB1 expression was even further decreased in COPD patients (0.32 ± 0.02), a statistically significant finding vs. both non-COPD smokers (P = 0.040) and non-smokers (P < 0.001). By contrast, PHB2 levels were similar among the three study groups. Western blot analysis for the PHB1 protein verified the qPCR results (non-smokers: 1.77 ± 0.13; non-COPD smokers: 0.97 ± 0.08; COPD patients: 0.59 ± 0.10, P = 0.007). Further analysis revealed that PHB1 downregulation in COPD patients cannot be attributed solely to smoking, and that PHB1 expression levels are associated with the degree of airway obstruction [FEV1 (PmRNA = 0.004, Pprotein = 0.014)]. The significant downregulation of PHB1 in COPD and non-COPD smokers in comparison to non-smokers possibly reflects a distorted mitochondrial function due to decreased mitochondrial stability, especially in the mitochondria of COPD patients.

Daily step counts in a US cohort with COPD

Marilyn L. Moy, Valery A. Danilack, Nicole A. Weston, Eric Garshick — 2012-04-23

Summary: Background: Baseline values for daily step counts in US adults with COPD and knowledge of its accurate measurement, natural change over time, and independent relationships with measures of COPD severity are limited.Methods: 127 persons with stable COPD wore the StepWatch Activity Monitor (SAM) for 14 days, and 102 of them wore it a median 3.9 months later. SAM counts were compared to manual counts in the clinic. We assessed change over time, the effect of season, and relationships with forced expiratory volume in 1 s (FEV1) % predicted, 6-min walk test (6MWT) distance, the modified Medical Research Council (MMRC) dyspnea score, and the St. George's Respiratory Questionnaire Total Score (SGRQ-TS).Results: 98% of subjects were males, with mean age 71 ± 8 years and FEV1 1.48 ± 0.54 L (52 ± 19% predicted). All 4 GOLD stages were represented, with the most subjects in GOLD II (44%) and GOLD III (37%). The SAM had >90% accuracy in 99% of subjects. Average step count was 5680 steps/day, which decreased with increasing GOLD stage (p = 0.0046). Subjects walked 645 fewer steps/day at follow-up, which was partly explained by season of monitoring (p = 0.013). In a multivariate model, FEV1 % predicted, 6MWT distance and MMRC score were weakly associated with daily step counts, while SGRQ-TS was not.Conclusions: These findings will aid the design of future studies using daily step counts in COPD. Accurately measured, daily step counts decline over time partly due to season and capture unique information about COPD status.

A randomized, double-blind dose-ranging study of the novel LAMA GSK573719 in patients with COPD

2012-04-12

Summary: Background: This study evaluated the dose-response and dosing interval of the novel long-acting muscarinic receptor antagonist (LAMA) GSK573719 in patients with COPD.Methods: This randomized, double-blind, placebo-controlled, 3-way cross-over, incomplete block study evaluated 5 once-daily doses of GSK573719 (62.5–1000 μg), 3 twice-daily doses (62.5–250 μg), and open-label tiotropium for 14 days in patients (N = 176) with COPD (FEV1 of 35–70% predicted). The primary endpoint was morning trough FEV1 at Day 15. Secondary endpoints included 0–24 h weighted mean FEV1 and serial FEV1 values over 28 h. Safety measures and pharmacokinetics were assessed.Results: All once-daily doses of GSK573719 significantly increased trough FEV1 at Day 15 with improvements ranging from 95 to 186 mL over placebo (p ≤ 0.006), from 79 to 172 mL with twice-daily dosing (p ≤ 0.03), and 105 mL with tiotropium (p = 0.003). No clear dose ordering was observed. Once-daily doses significantly (p < 0.001) increased 0–24 h weighted mean FEV1 at Day 14 by 131–143 mL over placebo, comparable to increases with the twice-daily doses (120–142 mL) and tiotropium (127 mL). Significant reductions in rescue albuterol use and improvements in FVC were also observed with once-daily dosing. Plasma Cmax occurred within 5–15 min of dosing after which the drug was rapidly cleared and eliminated. GSK573719 was well tolerated, with no apparent treatment-related changes in vital signs, ECG and Holter assessments, or clinical laboratory parameters.Conclusion: Once-daily dosing with GSK573719 in COPD provides clinically significant and sustained improvement in lung function over 24 h with similar efficacy to twice-daily dosing.

COPD among non-smokers – Report from the Obstructive Lung Disease in Northern Sweden (OLIN) studies

2012-04-12

Summary: Background: In westernized countries smoking and increasing age are the most important risk factors for COPD. Prevalence and risk factors of COPD among non-smokers are not well studied.Aim: To study the prevalence and risk factors of COPD among non-smokers and to determine the proportion of non-smokers among subjects with COPD.Methods: A random sample of 2470 subjects drawn from a population-based postal survey of 10,040 (85–88% participation) adults (aged 20–77) in Norrbotten, Sweden, were invited to structured interviews and lung function tests, and 1897 participated. COPD was classified using the fixed ratio (GOLD) definition and for comparison the lower limit of normal (LLN).Results: The prevalence of airway obstruction was 6.9% among non-smokers and strongly age related. The prevalence of GOLD stage ≥II among non-smokers was 3.5%. Both among subjects with airway obstruction and among subjects with GOLD stage ≥II, the proportions of non-smokers were 20%. Of men with airway obstruction, 14.1% were non-smokers versus 26.8% among women. Non-smokers with GOLD stage ≥II had significantly more symptoms and higher co-morbidity than non-smokers without airway obstruction. Sex, area of domicile and exposure to environmental tobacco smoke was not significantly associated to airway obstruction among non-smokers. Using LLN for defining airway obstruction yielded a similar prevalence.Conclusion: The prevalence of airway obstruction among non-smokers was close to 7% and was associated with increasing age. One out of seven men with airway obstruction, defined using the fixed ratio, versus one out of four women had never smoked.

How far is real life from COPD therapy guidelines? An Italian observational study

Antonio Corrado, Andrea Rossi — 2012-04-06

Summary: Background: According to the GOLD international guidelines, the treatment of chronic obstructive pulmonary disease (COPD) should be proportional to the severity of airflow obstruction graded according to FEV1% predicted. Regular treatment with long-acting bronchodilators should be prescribed for symptomatic patients with FEV1 < 80%. Inhaled corticosteroids should be added in patients with FEV1 < 50% predicted and frequent exacerbations.Aim: To investigate whether pulmonologists follow the GOLD guidelines when prescribing treatment for COPD.Methods: A multicenter, cross-sectional, observational study was carried out in 49 Pulmonary Units evenly distributed throughout the country. For each patient the demographic, clinical data and the current therapies were registered in an electronic database.Results: 4094 patients (mean age: 70.9 ± 9.4; males 72.4%, female 27.6%) were enrolled. Disease severity was classified as: mild (745), moderate (1722), severe (923), very severe (704). Irrespective of disease severity, inhaled corticosteroids alone or in combination with long-acting bronchodilators were used in 15.2% and 66.8% of patients, respectively. The appropriateness of the pharmacological treatment of the COPD patients was defined in accordance with the GOLD recommendations. The treatment was appropriate in 37.9% of patients and inappropriate in 62.1%, p < 0.0001. The inappropriateness was due to under-prescription in 7.2% and to over-prescription in 54.9% of patients. The presence and the number of exacerbations represented an important trigger for over-prescription at stages I and II.Conclusions: This study shows that there is a poor relationship between the recommendations of the GOLD international guidelines and current clinical practice, and that exacerbations may play a role in over-prescription.

Pain in people with chronic obstructive pulmonary disease (COPD)

Bahareh HajGhanbari, Liisa Holsti, Jeremy D. Road, W. Darlene Reid — 2012-04-23

Summary: Introduction: The prevalence and characteristics of pain are not known in COPD patients. The purposes of this study were to determine if pain is more common in COPD patients than in healthy people and if it was related to self-reported physical activity, health related quality of life (HRQoL) and comorbidities.Methods: Participants returned a mailed survey package that contained: 1) McGill Pain Questionnaire (MPQ) and Brief Pain Inventory (BPI) to evaluate pain severity and how pain interferes with activities; 2) Tampa Scale for Kinesiophobia (TSK) to evaluate fear of movement related to pain; 3) Short Form-36 (SF-36), to measure HRQoL; 4) Community Health Activities Model Program for Seniors (CHAMPS) to evaluate physical activity; 5) a form to list medications and comorbidities.Results: Forty-seven COPD patients and 47 age- and gender-matched healthy people responded. People with COPD demonstrated more pain (MPQ and BPI, p = 0.000), a greater pain-related interference in their lives (BPI, p = 0.000), a higher pain-related fear of movement, and lower frequency and energy expenditure of physical activities (CHAMPS, p = 0.000) than healthy people (TSK, p < 0.001). Pain severity (MPQ and BPI) was indirectly correlated to the Physical Component Score of the SF-36. COPD patients identified pain in the neck and trunk 3.1 times more often than healthy people. The number of comorbidities was the most consistent independent correlate of pain in COPD patients.Conclusions: COPD patients demonstrate more pain which interferes with activities more so than healthy people of similar age. Pain is also negatively associated with HRQoL in COPD.

Respiratory movement and pain thresholds in airway environmental sensitivity, asthma and COPD

Ewa-Lena Johansson, Ewa Ternesten-Hasséus, Monika Fagevik Olsén, Eva Millqvist — 2012-04-17

Summary: Introduction: Patients with “sensory hyperreactivity” (SHR) have airway environmental sensitivity, chronic cough and dyspnoea. Cough, chest discomfort and sense of difficulties getting air are some of the symptoms these patients seek medical attendance for. The patients have increased cough sensitivity to inhaled capsaicin, mediated by ion channel receptors on sensory nerves also known to react to pain stimuli. Whether a link exists between capsaicin airway sensitivity and pain sensitivity has not yet been evaluated. The aim was to investigate chest mobility, respiratory movement and pain sensitivity in SHR patients compared with patients with asthma, chronic obstructive pulmonary disease (COPD) and alleged healthy control subjects.Methods: Thirty-five patients diagnosed with SHR, 19 with COPD, 32 with asthma and 28 control subjects were included. Chest expansion was measured with a measuring tape and thoracic and abdominal movement with light sensors. Pain sensitivity was assessed using a pressure algometer.Results: Groups differed significantly in lung function, respiratory rate and pain sensitivity but also in chest expansion and abdominal breathing movement. In comparison with the control and asthma groups but not the COPD patients, SHR patients had an increased respiratory rate and reduced abdominal movement during deep breathing. All patient groups showed lower pain thresholds than the controls.Conclusion: Patients with SHR have evident signs of dysfunctional breathing and appeared to be most similar to the COPD group except for lung function. Lower pain thresholds among the patients indicate a general up-regulation of the sensory nerve system.

Diagnostic value of CD103 expression in bronchoalveolar lymphocytes in sarcoidosis

2012-04-26

Summary: Background: Pulmonary sarcoidosis is frequently characterized by a CD4+/CD8+ ratio ≥3.5 in bronchoalveolar lavage fluid (BALF), although up to 40% of the cases present a normal or even decreased ratio, pointing out its variability and limitation as a diagnostic marker for sarcoidosis. Lung lymphocytes within the bronchial epithelium, the alveolar walls, and BALF express the integrin CD103. Our aim was to compare the expression of CD103 in BALF T-lymphocytes between sarcoidosis and other interstitial lung diseases (ILD) and to evaluate its relevance as a BALF diagnostic marker for sarcoidosis.Methods: A total of 86 patients with ILD (mean age ± standard deviation, 42.6 ± 16.6 years; 60.5% female), who underwent BALF as part of their initial diagnostic work-up, were enrolled into 2 groups: sarcoidosis (n = 41) and other ILD (n = 45). Area under the receiver operating characteristic (ROC) curve (AUC) was used to describe the performance of CD103 for sarcoidosis diagnosis.Results: Sarcoidosis patients presented a significantly reduced CD103 expression in BALF T-lymphocytes, more pronounced in the CD4+ subset. The BALF CD103+CD4+/CD4+ ratio for a cutoff point of 0.45 was associated with a better diagnostic performance for sarcoidosis (AUC: 0.86 [95% confidence interval (95% CI): 0.78–0.94]; sensitivity: 81%; specificity: 78%), even for those with a CD4+/CD8+ ratio <3.5 (AUC: 0.79 [95% CI: 0.64–0.93]; sensitivity: 75%; specificity: 78%).Conclusions: Assessment of CD103 expression in BALF CD4+ T-lymphocytes may be a reliable tool for sarcoidosis diagnosis, independently of CD4+/CD8+ ratio, pointing out the relevance of evaluating the CD103+CD4+/CD4+ ratio in the ILD diagnostic work-up.

Diffuse alveolar hemorrhage in immunocompetent patients: Etiologies and prognosis revisited

2012-04-27

Summary: Background: Diffuse alveolar hemorrhage (DAH) represents a diagnostic challenge of acute respiratory failure. Prompt identification of the underlying cause of DAH and initiation of appropriate treatment are required in order to prevent acute respiratory failure and irreversible loss of renal function. More than 100 causes of DAH have been reported. However, the relative frequency and the differential presentation of those causes have been poorly documented, as well as their respective prognosis.Methods: We retrospectively reviewed the charts of 112 consecutive patients hospitalized for DAH in a tertiary referral center over a 30-year period.Results: Twenty-four causes of DAH were classified into four etiologic groups: immune (n = 39), congestive heart failure (CHF; n = 33), miscellaneous (n = 26), and idiopathic DAH (n = 14). Based on this classification, clinical and laboratory features of DAH differed on hospital admission. Patients with immune DAH had more frequent pulmonary-renal syndrome (p 200 mL (p < 0.05). Patients with idiopathic DAH had more bronchoalveolar lavage siderophages (p < 0.01). In-hospital mortality was 24.1%, ranging from 7.1% in patients with idiopathic DAH to 36.4% in those with CHF.Conclusions: Arbitrary classification of DAH in four etiologic groups gives the opportunity to underline distinct presentations and outcomes of various causes of DAH.

Obstructive sleep apnea does not promote esophageal reflux in fibrosing interstitial lung disease

2012-04-23

Summary: Background: In patients with fibrosing interstitial lung disease (fILD), gastroesophageal reflux (GER) is highly prevalent, perhaps because of the effects of lung fibrosis on altering intrathoracic pressure, diaphragm morphology and lower esophageal sphincter (LES) function. For unclear reasons, obstructive sleep apnea (OSA) is also highly prevalent among patients with fILD. We conducted this study to test our hypothesis that, in patients with fILD, OSA would exacerbate diaphragm/LES dysfunction and increase the propensity for—and severity of – GER.Methods: We identified patients with fILD who underwent screening polysomnogram and pH or pH/impedence probe at our center during the same week. We examined the association between OSA and GER and used logistic regression to determine independent predictors of OSA or GER.Results: In 54 included subjects, neither OSA (dichotomous) nor apnea hypopnea index (continuous) predicted the presence of GER. Regardless of body position (upright, recumbent), GER was no more frequent or severe among subjects with OSA vs. those without OSA. Subjects with idiopathic pulmonary fibrosis (IPF) had an odds of GER nearly seven-fold greater than subjects with other forms of fILD (odds ratio = 6.84, 95% confidence interval 1.36–34.43, p = 0.02). For the entire cohort and the subgroup with IPF, there was no correlation between pulmonary physiology and GER.Conclusions: In fILD, OSA does not appear to promote GER. Research is needed to determine if compensatory mechanisms emanating from the crural diaphragm prevent GER in fILD patients with OSA and to sort out whether GER has a role in the pathogenesis of certain forms of fILD.

Lung disease with anti-CCP antibodies but not rheumatoid arthritis or connective tissue disease

2012-04-16

Summary: Objective: We sought to characterize a novel cohort of patients with lung disease, anti-cyclic citrullinated peptide (CCP) antibody positivity, without rheumatoid arthritis (RA) or other connective tissue disease (CTD).Methods: The study sample included 74 subjects with respiratory symptoms, evaluated January 2008–January 2010 and found to have a positive anti-CCP antibody but no evidence for RA or other CTD. Each underwent serologic testing, pulmonary physiology testing, and thoracic high-resolution computed tomography (HRCT) scan as part of routine clinical evaluation.Results: The majority of subjects were women, and most were former cigarette smokers. Four distinct radiographic phenotypes were identified: isolated airways disease (54%), isolated interstitial lung disease (ILD) (14%), mixed airways disease and ILD (26%), and combined pulmonary fibrosis with emphysema (7%). This cohort had a predominance of airways disease, either in isolation or along with a usual interstitial pneumonia-pattern of ILD. Among subjects with high-titer anti-CCP positivity (n=33), three developed the articular manifestations of RA during a median follow-up of 449 days.Conclusion: We have described a unique cohort of patients with anti-CCP antibody positivity and lung disease in the absence of existing RA or other CTD. The lung phenotypic characteristics of this cohort resemble those of established RA and a few of these patients have developed articular RA within a short period of follow-up. The implications of a positive anti-CCP antibody among patients with lung disease but not RA are not yet known, but we believe requires further investigation.

Low prevalence of pulmonary involvement in children with inflammatory bowel disease

2012-04-20

Summary: Background: Since extraintestinal sites of inflammation have been demonstrated in patients with Crohn's disease (CD) and ulcerative colitis (UC), both entities are regarded as systemic disorders. There are only scarce data on the prevalence of inflammatory bowel disease (IBD)-associated lung involvement in children.Objectives: The aim of our study was to investigate pulmonary involvement in pediatric patients with IBD.Material and methods: Fifty children with IBD (25 UC and 25 CD, mean age 14.2 ± 3.2 yrs) and 39 age-matched, healthy, control subjects were included in the study. Pulmonary function testing, methacholine bronchial challenge, fractional exhaled nitric oxide (FeNO) and high resolution computed tomography (HRCT) were used to detect functional and/or structural pulmonary involvement.Results: There were no differences in spirometric parameters, lung volumes or lung diffusion capacity for carbon monoxide between IBD patients and control subjects. Highly significant differences were found in FeNO between CD, UC and control patients (mean 9.3 ± 3.3, 27.7 ± 14.8 and 16.6 ± 9.28, respectively; p = 0.000). Bronchial hyperresponsiveness was diagnosed in six IBD cases (14.6%). HRCT (performed in 32 patients from the study group) revealed mild bilateral bronchiectasis in one patient.Conclusions: The prevalence of pulmonary involvement in children with IBD is low. Screening for pulmonary involvement in children and young adults with IBD may enable early detection of IBD-related pulmonary diseases which, seems to be notably more common in adult patients. Elevated FeNO could probably be regarded as a marker of airway involvement in non-smoking UC pediatric patients. This requires further studies.

Smoking cessation and the risk of hospitalization for pneumonia

2012-04-27

Summary: Background: Smoking increases the risk of hospitalization for pneumonia, yet it is unknown if smoking cessation changes this risk. We sought to determine if smoking cessation and the duration of abstinence from tobacco reduce the risk of pneumonia hospitalization.Methods: We performed secondary analysis of data collected from male United States Veterans participating in a randomized trial. We used Cox proportional-hazard models to estimate risk of hospitalization for pneumonia within one year of enrollment. We adjusted for confounders, including: demographics, comorbidity, alcohol use, prior pneumonia, inhaled corticosteroid use, and intensity of tobacco exposure. Among a restricted cohort excluding never smokers, we assessed for effect modification by a diagnosis of chronic obstructive pulmonary disease (COPD).Results: Of the 25,235 participants, we identified 6720 current, 13,625 former, and 4890 never smokers. Compared to current smokers, never smokers had a decreased (adjusted HR 0.48, 95% CI 0.31–0.74), while former smokers had no difference in (adjusted HR 0.83, 95% CI 0.63–1.09) risk of hospitalization for pneumonia. Among participants without COPD, former smokers had a lower risk of hospitalization (adjusted HR 0.65, 95% CI 0.45–0.95). However, this lower risk was isolated to those who quit tobacco more than 10 years previously (adjusted HR 0.62, 95% CI 0.41–0.93). Among those with COPD, there was no difference in risk with smoking cessation or duration of remaining tobacco-free.Conclusions: Tobacco cessation is likely important in reducing hospital admissions for pneumonia, but its benefit depends on duration of smoking cessation and is likely attenuated in the presence of COPD.

External beam radiation therapy is safe and effective in treating primary pulmonary amyloidosis

Shaohua Ren, Gang Ren — 2012-03-14

Summary: The aim of the prospective study was to explore the safety and effectiveness of external beam radiation therapy (EBRT) in three patients with biopsy proven primary pulmonary amyloidosis, including two tracheobronchial amyloidosis patients and one primary parenchymal amyloidosis patient. All three patients were treated to 24Gy in 12 fractions utilizing CT simulation and 3-D planning. All three patients had significant improvement in clinical symptoms, radiological imaging as well as pulmonary function tests. The improvement in the clinical symptoms was evident in 2 days. Toxicities related to EBRT were not observed during the follow-up range from 42 to 54 months. EBRT to 24Gy was safe and effective in the three patients with primary pulmonary amyloidosis, and resulted in rapid relief of pulmonary symptoms.