Irreversiblity of Remodeled Features on High-Resolution Computerized Tomography Scans of Asthmatic Patients on Conventional Therapy: A 6-Year Longitudinal Study

Airway remodeling can be assessed using high-resolution computerized tomography (HRCT) scanning of both parenchymal-and airway abnormalities in patients with asthma. The aim of this study was to examine structural changes in large and small airways of asthmatic patients using HRCT to determine if remodeling changes had occurred after prolonged use of conventional anti-asthma therapy. HRCT scans were evaluated prospectively for evidence of the following abnormalities: bronchial wall thickening (BWT), bronchiectasis, mucoid impactions, small centrilobular opacities, thick linear opacities, focal hyperlucency, and emphysema. Fifty mild and moderate asthmatics were enrolled in the study group. These abnormalities were re-evaluated in the patients after the passage of 6 years of regular anti-asthma medication. Forty-six of the patients completed the study. The probability of finding at least one abnormality by HRCT investigation was statistically higher in the second scan than in the first (26 patients [56.5%] versus 18 patients [39.1%], p = 0.02]. Irreversibility ratios of abnormalities were 80%, 100%, 75%, 87.7%, 77.8%, and 100% for BWT, bronchiectasis, small centrilobular opacities, focal hyperlucency, thick linear opacity, and emphysema, respectively. The ratios for newly detected structural abnormalities were 25%, 2.5%, 0%, 7.9%, 8.1%, and 0% for BWT, bronchiectasis, small centrilobular opacities, focal hyperlucency, thick linear opacity, and emphysema, respectively. New occurrences and progression in BWT are associated with the duration of asthma affliction (p = 0.03). The results of our study indicate that HRCT remodeling features, once occurring, are irreversible in most of the patients, and new remodeling features also occur despite administering the standard asthma treatment.     

Distribution of alpha(1)-antitrypsin alleles in patients with bronchiectasis

STUDY OBJECTIVES: Bronchiectasis has been reported in a few patients with homozygous alpha(1)-antitrypsin (AAT) deficiency, but the distribution of AAT alleles among bronchiectatic patients is not known. Patients and design: Two hundred two patients, 104 men and 98 women, with a mean age (SD) of 63.7 +/- 15.4 years, had bronchiectasis diagnosed by CT scan alone (n = 178), bronchography with or without CT scan (n = 17), or radiography alone (n = 7). AAT phenotypes (classified according to the protease inhibitor [PI] system) were determined by isoelectric focusing in blood samples obtained from all patients. Bronchiectasis was primary in 121 cases and secondary in 81 patients. Allele and phenotype frequencies were compared retrospectively between bronchiectatic patients and healthy blood donors living in the same geographic area. RESULTS: The PI phenotype frequencies among patients were the following: MM, 81.18%; MS, 11.88%; MZ, 3.46%; IZ, 0.49%; IM, 0.49%; SS, 1.48%; SZ, 0.49%; and ZZ, 0.49%. The allelic frequencies among patients were the following: M, 89.1%; S, 7.67%; Z, 2.72%; and I, 0.49%. There was no difference in the distribution of alleles or phenotypes either between patients and control subjects or between patients with secondary and primary bronchiectasis. A significant difference was found between bronchiectatic patients with and without coexisting emphysema (p = 0.028). This difference was caused by an overrepresentation of PI*Z alleles in bronchiectatic patients with coexisting emphysema. CONCLUSIONS: Our results do not support a physiopathologic implication of the AAT genes in the development of bronchiectasis. We suggest that bronchiectasis may be a consequence of emphysema in PI*Z patients rather than a primary effect.     

Early Exacerbation Relapse is Increased in Patients with Asthma and Bronchiectasis (a Post hoc Analysis)

Purpose

Asthma is a common comorbidity in patients with bronchiectasis and has been shown to increase the risk of bronchiectasis exacerbations. This paper explores the impact of comorbid asthma on patients receiving intravenous antibiotic treatment for bronchiectasis exacerbations.

Methods

This was a post hoc analysis of the Meropenem randomised controlled trial of 90 patients that had intravenous antibiotic treatment for bronchiectasis exacerbations. The participants were split into two groups: group 1 (asthma and bronchiectasis) and group 2 (bronchiectasis). The authors assessed response to treatment and time to next exacerbation.

Results

There were 38 participants in group 1 and 34 participants in group 2. The groups were found to be comparable in terms of age, sex, and bronchiectasis severity (median (95% CI) group 1 and then group 2 data): age 64.0(59.3, 68.6) and 63.6(57.9, 69.4) years old, p?=?0.8; 57.9% and 64.7% female, p?=?0.6; Bronchiectasis Severity Index 11.1(9.8, 12.4) and 10.1(8.2, 12.0), p?=?0.3. There was a similar response to treatment between the groups, but group 1 were found to relapse early by day 14, 31.6% in group 1 and 11.8% in group 2, p?=?0.03. In the Cox proportional hazards model, asthma was the only independent risk factor for early relapse by day 14 (odds ratio (95% CI) 3.16 (1.02–9.79), p?=?0.047).

Conclusion

The clinical response to treatment was similar but patients with coexisting asthma were at increased risk of early relapse within 14 days of stopping intravenous antibiotic therapy. Clinical Trial Registration: NCT02047773.

     

慢性阻塞性肺疾病合并支气管扩张危险因素分析

目的探讨慢性阻塞性肺疾病(COPD)合并支气管扩张患者的临床特点及危险因素。方法收集河南省人民医院呼吸内科2016年1月至2018年5月住院诊断为中度以上COPD患者173例,其中69例患者行胸部高分辨率CT(HRCT)检查诊断合并支气管扩张,作为病例组;另104例患者行HRCT检查未合并支气管扩张(对照组)。整理两组患者首诊时病例资料,如性别、年龄、吸烟史、吸烟年限、慢阻肺评估测试问卷(CAT)评分、GOLD分级、慢性呼吸道症状(咳嗽、咳痰、呼吸困难)出现时间、既往肺结核史、既往糖尿病史、血糖、血红蛋白(Hb)、总蛋白(TP)、痰培养细菌学结果等。分析慢性阻塞性肺疾病合并支气管扩张患者的临床特点,评估易合并支气管扩张的相关因素。结果慢性阻塞性肺疾病合并支气管扩张占39.9%,大多为男性(P=0.017),有吸烟史(P=0.037),吸烟年限更长(P=0.035),CAT评分更高(P=0.002),GOLD分级更重(P=0.031),慢性呼吸道症状时间更长(P=0.001),既往有结核病史(P=0.044),既往有糖尿病史(P=0.003),血糖更高(P=0.003);多因素logistic回归分析显示与COPD合并支气管扩张的危险因素有男性(OR 2.427,95%CI 1.126~5.231,P=0.024)、CAT分(OR 1.476,95%CI 1.031~2.113,P=0.034)、慢性呼吸道症状时间(OR 3.502,95%CI 1.619~7.575,P=0.001)、既往糖尿病史(OR 4.182,95%CI 1.407~12.427,P=0.010)。结论慢性阻塞性肺疾病患者为男性、CAT评分越高、慢性呼吸道症状时间持续越长、既往有结核病史和糖尿病史时易合并支气管扩张,应得到重视,尽早明确诊断给予治疗。     

Clinical Value of Ciliary Assessment inBronchiectasis

Although ciliary dysfunction and numerous ultrastructural defects have been described, and these could be etiologically important in the development of bronchiectasis, their correlation with relevant clinical parameters have not been systematically evaluated. We have prospectively evaluated the prevalence and clinical significance of ciliary beat frequency and ultrastructural defects of nasal respiratory mucosa obtained from 152 stable patients with idiopathic bronchiectasis (100F, 57.7±15.2 yrs) and 127 control subjects (58F, 56.0±24.2 yrs). Bronchiectasis patients had significantly slower ciliary beat frequency (p < 0.05), and a greater percent of patients had central and peripheral microtubular defects (OR 14.4, 95% CI 5.6-36.8), namely, extra peripheral microtubules, “9+1”, “8+2”, and compound cilia (p < 0.05), but not microtubular disarrangement, extra matrix or ciliary tail abnormalities (p > 0.05), than controls. Bronchiectasis patients also had a greater proportion of cilia with any ultrastructural microtubular defects, compound cilia, and ciliary tails than controls (p < 0.05). Ciliary beat frequency did not correlate with clinically relevant parameters (p > 0.05). However, the percent of cilia with central, but not peripheral, microtubular defects correlated with 24 h sputum volume (r = 0.40, p = 0.001, and r = −0.04, p = 0.70, respectively) and FEV₁ (r = −0.24, p = 0.01, and r = 0.00, p =0.99 respectively). Our results strongly suggest a pathogenic role for central microtubular defects in the development of idiopathic bronchiectasis.     

Usefulness of the CAT,LCOPD, EQ-5D and COPDSS Scales in Understanding the Impact of Lung Disease in Patients with Alpha-1 Antitrypsin Deficiency

Alpha-1-antitrypsin deficiency (AATD) is an inherited disorder responsible for early onset emphysema associated with a significant impairment of health-related quality of life (HRQoL). Our aim was to assess the usefulness of different instruments to evaluate the HRQoL in patients with AATD compared to non-AATD COPD. Observational, cross-sectional study in which all patients filled out a series of questionnaires: the COPD severity score (COPDSS), the EuroQoL 5-Dimensions (EQ-5D), the Living with COPD (LCOPD) and the COPD Assessment Test (CAT).

A total of 96 patients were included, 35 with AATD (mean age 56.5 yrs, 57.1% male and mean FEV₁(%) 48.7% and 61 non-AATD COPD (70.3 yrs, 80.3% men and FEV₁(%) 47%. The questionnaire scores were similar, with a tendency towards worse scores in AATD for the EQ-5D (VAS) (64.8 (20.2) vs. 71.6 (17.1); p = 0.08). The correlations between the different scores and FEV1(%) were significant in both groups for COPDSS and LCOPD, but not for CAT and EQ-5D. In general, the correlations of scores with FEV₁(%) were stronger for AATD compared with non-AATD COPD patients: COPDSS r = ?0.570, p < 0.01 for AATD and r = ?0.260, p < 0.05 for COPD; LCOPD r = ?0.502, p < 0.001 for AATD and r = ?0.304, p < 0.05 for non-AATD COPD.

Patients with AATD have a similar degree of HRQoL impairment as older subjects with non-AATD COPD and showed a stronger correlation between HRQoL measurements and lung function impairment compared with non-AATD COPD. This may be related to the characteristics of the disease in these patients who are usually younger, with less co-morbidity and lower smoking consumption.     

The extent of emphysema in patients with COPD

Background and Aims: The global initiative for COPD (GOLD) adopted the degree of airway obstruction as a measure of the severity of the disease. The objective of this study was to apply CT to assess the extent of emphysema in patients with chronic obstructive pulmonary disease (COPD) and relate this extent to the GOLD stage of airway obstruction. Materials and Methods: We included 209 patients with COPD. COPD was defined as FEV₁/FVC < 0.70 and no reversibility to β₂‐agonists. All patients were current smokers with a smoking history of ≥20 pack‐years. Patients were assessed by lung function measurement and visual and quantitative assessment of CT, from which the relative area of emphysema below ?910 Hounsfield units (RA‐910) was extracted. Results: Mean RA‐910 was 7.4% (n = 5) in patients with GOLD stage I, 17.0% (n = 119) in stage II, 24.2% (n = 79) in stage III and 33.9% (n = 6) in stage IV. Regression analysis showed a change in RA‐910 of 7.8% with increasing severity according to GOLD stage (P < 0.001). Combined visual and quantitative assessment of CT showed that 184 patients had radiological evidence of emphysema, whereas 25 patients had no emphysema. Conclusion: The extent of emphysema increases with increasing severity of COPD and most patients with COPD have emphysema. Tissue destruction by emphysema is therefore an important determinant of disease severity in COPD. Please cite this paper as: Shaker SB, Stavngaard T, Hestad M, Bach KS, Tonnesen P and Dirksen A. The extent of emphysema in patients with COPD. The Clinical Respiratory Journal 2009; 3: 15–21.     

Clinical analysis of chronic obstructive pulmonary disease phenotypes classified using high-resolution computed tomography

OBJECTIVE AND BACKGROUND: The present study was performed to clarify the clinical characteristics of patients with COPD classified into phenotypes according to the dominancy of emphysema and the presence of bronchial wall thickening (BWT) evaluated by chest high-resolution CT. METHODS: A total of 172 patients with stable COPD (FEV1<80%) were examined by chest high-resolution CT. Emphysematous changes and BWT were evaluated visually, and COPD patients were classified into three phenotypes: absence of emphysema, with little emphysema with or without BWT (A phenotype), emphysema without BWT (E phenotype) and emphysema with BWT phenotype (M phenotype). The clinical characteristics were compared among the three phenotypes. RESULTS: The A phenotype showed a higher prevalence of those who had never smoked and patients with wheezing both on exertion and at rest, higher values of BMI and diffusing capacity for carbon mononide (DLCO), milder lung hyperinflation, and greater reversibility of airflow limitation responsive to beta2-agonist as compared with the E phenotype. The M phenotype showed a higher prevalence of patients complaining of a large amount of sputum, productive cough and wheezing, higher rate of exacerbation or hospitalization and greater reversibility of airflow limitation responsive to beta2-agonist as compared with the E phenotype. CONCLUSIONS: These findings suggest that the morphological phenotypes of COPD show several clinical characteristics and different responsiveness to bronchodilators.     

Does coexistence with bronchiectasis influence intensive care unit outcome in patients with chronic obstructive pulmonary disease?

BACKGROUND: Bronchiectasis is associated with chronic obstructive pulmonary disease (COPD) in 30% to 50% of patients. This study evaluated whether association with bronchiectasis has any influence on morbidity and mortality in patients with COPD during their intensive care unit (ICU) stay. METHODS: The study was conducted at a respiratory ICU of a university hospital, and 93 mechanically ventilated patients with COPD were studied. Twenty-nine (31%) of 93 patients with COPD also had bronchiectasis. Patients with bronchiectasis had more frequent hospitalizations, more severe airflow limitation, and higher pulmonary artery pressure than patients without bronchiectasis. Duration of ICU (27+/-32 days [median: 14]; 16+/-16 days [median: 9]; P=.01) and hospital stays (44+/-44 days [median: 24.5]; 28+/-26 days (median: 20); P=.046) in patients with bronchiectasis were significantly longer than in patients without bronchiectasis, respectively. Bronchiectasis was an independent predictor for ICU stay longer than 10 days (odds ratio: 5, 95% confidence interval: 1.02-21, P=.043). The development rate of ventilator-associated pneumonia, especially with Pseudomonas aeruginosa, was significantly higher in patients with bronchiectasis (P=.034). Despite these prolonged durations, bronchiectasis did not increase mortality in this study population (P=.865). RESULTS: These results suggest that the coexistence of bronchiectasis in patients with COPD may increase the duration of ICU stay and hospitalization but does not influence the mortality.     

Asthma,COPD and comorbidities in elderly people

Co-morbidities are a significant problem in the elderly population but are rarely presented and analyzed for interdependencies among the various coexisting chronic diseases. Objective: The aim of this study was to present a profile of comorbidities in elderly patients with and without asthma and COPD. Methods: Respondents were recruited at 20 sites in Poland. Stratified random sampling from patient databases resulted in 15,973 patients older than 60 years of age. A retrospective analysis of medical history and ICD-10 codes was performed. In addition, patients underwent a spirometry test with a bronchial reversibility test and were administered questionnaires on the prevalence of chronic diseases by doctors. Results: The study population consisted of 1023 asthmatic patients, 1084 patients with COPD and 1076 control subjects without any signs of bronchoconstriction and with correct spirometry. Patients with asthma exhibited a similar distribution of cardiovascular and metabolic co-morbidities as the control group. However, asthmatic patients had a higher prevalence of arterial hypertension and depression with an odds ratio (OR) = 1.48 (95% CI: 1.38–1.62) and OR = 1.52 (95% CI: 1.44–1.68), respectively. Coronary disease (OR = 2.12; 95% CI: 1.97–2.33), cor pulmonale (OR = 3.1; 95% CI: 2.87–3.22) and heart failure (OR = 2.71; 95% CI: 2.64–3.11) were predominantly observed in patients with COPD. Patients with severe asthma exhibited a greater predisposition to cardiovascular and neuropsychiatric diseases. Conclusion: Asthma coexisted frequently with arterial hypertension and depression in elderly patients. Patients with COPD have a more exaggerated profile of coexisting diseases, specifically cardiovascular problems.     

Socioeconomic deprivation, readmissions, mortality and acute exacerbations of bronchiectasis

Background: Bronchiectasis is known to cause significant morbidity in children in New Zealand. Little is known of the disease in adults. Aim: Our objective was to characterise a cohort of adults who presented to hospital with acute exacerbations of the disease. Methods: We retrospectively collected information on all exacerbations treated as inpatients from a single hospital in South Auckland, New Zealand during 2002. Results: We collected information on 307 exacerbations in 152 patients. Twenty‐seven per cent were of Maaori ethnic origin, and 44% Pacific. Seventy per cent lived in areas categorised as the 20% most deprived in New Zealand. Comorbid conditions were present in 80% of patients – most commonly chronic obstructive pulmonary disease, asthma, diabetes and cardiac disease. Seventy (46%) patients had at least one readmission and 32 patients (21%) died within 12 months of admission to hospital. Greater deprivation was associated with increased mortality at 12 months after admission after adjusting for other factors (OR 11, 95% CI 2.0–61, P= 0.006). In the subgroup who underwent high‐resolution computed tomographic scanning (93), increasing severity of bronchiectasis (modified Bhalla score) was associated with readmission within 12 months (P= 0.004), but not mortality (P= 0.419). Conclusions: We have shown that exacerbations of bronchiectasis in South Auckland are more common in patients who are predominantly of Maaori or Pacific descent and are socioeconomically deprived. Admission to hospital for an exacerbation is associated with high readmission and mortality rates.     

Lung structure abnormalities, but normal lung function in pediatric bronchiectasis

BACKGROUND: Bronchiectasis is not considered to be uncommon in children anymore. The relationship between pulmonary function and severity of bronchiectasis is still controversial. STUDY OBJECTIVES: To assess the extent and severity of bronchiectasis through high-resolution CT (HRCT) scan score, and to correlate it with clinical, microbiological, and functional data. PATIENTS AND METHODS: Forty-three white children with HRCT-diagnosed bronchiectasis were studied. Bronchiectasis extent, bronchial wall thickening severity, and bronchial wall dilatation severity were evaluated using the Reiff score. Clinical, microbiological, and spirometry results were related to total HRCT scan score and to subscores as well. RESULTS: The percentages of affected lobes were as follows: right lower lobe, 65%; middle lobe, 56%; left lower lobe, 51%; right upper lobe, 37%; lingula, 30%; and left upper lobe, 30% (chi(2) = 18.4; p = 0.002). The mean (+/- SEM) HRCT score was 20 +/- 2.6. Total score or subscores of bronchiectasis extent, bronchial wall thickening severity, and bronchial wall dilatation severity were not significantly related to FEV(1) and FVC. Seventy-four percent of patients had asthma. The age at the onset of cough correlated with age at the time of the HRCT scan (p = 0.004) and with the presence of asthma (p = 0.01). Positive findings of deep throat or sputum cultures were found more frequently in atopic patients (p = 0.02) and asthmatic (p < 0.01) patients, and in children who were < 2 years of age at the onset of cough (p < 0.01). CONCLUSIONS: Normal lung function may coexist with HRCT scan abnormalities and does not exclude damage to the bronchial structure. Pulmonary function is not an accurate method for assessing the severity of lung disease in children with bronchiectasis.     

Gender differences in clinical characteristics of patients with non-cystic fibrosis bronchiectasis in different age groups in northern China

Introduction

Patient gender has clinical and prognostic implications in non-cystic fibrosis bronchiectasis, yet the potential effect of gender on clinical characteristics of patients with non-cystic fibrosis bronchiectasis is still unclear.

Objectives

This study aimed to investigate the gender differences in clinical characteristics of patients with bronchiectasis in different age groups in northern China.

Methods

A total of 777 patients diagnosed with bronchiectasis were retrospectively included in Beijing Chaoyang Hospital and divided into two groups by gender: the male group and the female group. Each group was then subdivided into two according to their age (≤65 and >65 years). Gender differences in clinical characteristics were compared in all patients with bronchiectasis in the two age groups, respectively.

Results

A total of 777 bronchiectasis patients were included. Of these patients, the prevalence of female non-smokers was substantially higher than that of male non-smokers (94.0% vs. 36.8%). There were gender differences in etiology of bronchiectasis, with more post-measles and connective tissue disease in females (p = 0.006 and 0.002 separately) and more chronic obstructive pulmonary disease (COPD) in males (p < 0.001). The male group had a significantly higher C-reactive protein (CRP) on admission (p = 0.03). Female patients showed a higher forced expiratory volume in 1 s as percentage of predicted volume (FEV1%pred) and forced vital capacity rate of 1 s (FEV1/FVC) (p < 0.001), lower partial pressure of carbon dioxide (PaCO₂) (p = 0.04) and hospital costs (p = 0.02) than males, and a higher prevalence of infection with Pseudomonas aeruginosa in >65-year-old group (p = 0.019).

Conclusions

There were many differences between male and female patients in smoking status, etiology, lung function, blood gas analysis, and hospital costs in all patients or different age groups.     

Genetic Variants in IL6R and ADAM19 are Associated with COPD Severity in a Mexican Mestizo Population

Chronic obstructive pulmonary disease (COPD) is a complex and multifactorial disease with a strong genetic component. Our objective is to identify the genetic variants associated with COPD risk and its severity in Mexican Mestizo population. We evaluated 1285 single-nucleotide polymorphisms (SNPs) of candidate genes in 299 smokers with COPD (COPD-S) and 531 smokers without COPD (SWOC) using an Illumina GoldenGate genotyping microarray. In addition, 251 ancestry informative markers were included. Allele A of rs2545771 in CYP2F2P is associated with a lower risk of COPD (p = 4.02E-10, odds ratio [OR] = 0.104, confidence interval [CI] 95% 0.05–0.18). When the COPD group was stratified by severity according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD; levels III + IV vs. I + II), 3 SNPs (rs4329505 and rs4845626 in interleukin 6 receptor [IL6R] and rs1422794 in a disintegrin and metalloproteinase domain 19 [ADAM19]) were associated with a lower risk of suffering the most severe stages of the disease. rs2819096 in the surfactant protein D (SFTPD) gene was associated with a higher risk of COPD GOLD III + IV (p = 7.79E-03, OR = 1.80, CI 95% 1.16–2.79). Finally, the haplotype in IL6R was associated with a lower risk of suffering from more severe COPD, whereas the haplotype in ADAM19 was associated with a higher risk (p = 7.40E-03, OR = 2.83, CI 95% 1.20–6.86) of suffering from the severe stages of the disease. Our data suggest that there are alleles and haplotypes in the IL6R, ADAM19, and SFTPD genes associated with different severity stages of COPD; in CYP2F2P, rs25455771 is associated with a lower risk of COPD.     

Six‐minute walk test in pulmonary rehabilitation: Do all patients need a practice test?

Background and objective: The six‐minute walk test (6MWT) is widely used as an outcome measure in pulmonary rehabilitation programs (PRP). A learning effect for the test has been reported in COPD; however, limited data exist in patients with other respiratory diagnoses. The objectives of this study were to: (i) report the magnitude of change in 6MWD with test repetition in patients referred to an outpatient PRP, and (ii) compare the magnitude of change in 6MWD with test repetition in patients with COPD, interstitial lung disease (ILD), bronchiectasis and asthma. Methods: Retrospective study of 349 patients with stable COPD (n = 245), ILD (n = 21), bronchiectasis (n = 33) or asthma (n = 50) who performed two 6MWT at enrolment into a PRP. Results: 6MWD increased in all groups on the second test (all P < 0.001). At least 80% of patients in each diagnostic group walked further on their second 6MWT. The magnitude of change (mean, 95% CI) was greater (P < 0.05) in the COPD (37 m, 95% CI: 33–41 m) and ILD (41 m, 95% CI: 27–55 m) cohorts compared with the bronchiectasis (22 m, 95% CI: 14–31 m) and asthma (19 m, 95% CI: 11–27 m) cohorts. Conclusions: Respiratory diagnosis influences the magnitude of the learning effect for the 6MWT. The findings support the recommendation of a practice 6MWT at baseline assessment in order to provide an accurate measure of the effects of rehabilitation on 6MWD.     

Mortality in Patients Admitted for Concurrent COPD Exacerbation and Pneumonia

It is unclear whether concurrent pneumonia and chronic obstructive pulmonary disease (COPD) have a higher mortality than either condition alone. Further, it is unknown how this interaction changes over time. We explored the effect of pneumonia and COPD on inpatient, 30-day and overall mortality. We used a Veterans Health Affairs database to compare patients who were hospitalized for a COPD exacerbation without pneumonia (AECOPD), patients hospitalized for pneumonia without COPD (PNA) and patients hospitalized for pneumonia who had a concurrent diagnosis of COPD (PCOPD). We studied records of 15,065 patients with the following primary discharge diagnoses: (a) AECOPD cohort (7,154 individuals); (b) PNA cohort (4,433 individuals); and (c) PCOPD (3,478 individuals), comparing inpatient, 30-day and overall mortality in the three study cohorts. We observed a stepwise increase in inpatient mortality for AECOPD, PNA and PCOPD (4.8%, 9.5% and 13.2%, respectively). These differences persisted at 30 days post-discharge (AECOPD = 6.7%, PNA = 12.4% and PCOPD = 14.6%; p < 0.0001), but not throughout the study period (median follow-up: 37 months). With time, the death rate rose disproportionally in patients who had been admitted for AECOPD (AECOPD = 64.5%; PNA = 57.4% and PCOPD 66.2%; p < 0.001). In multivariate analysis, PCOPD predicted the greatest inpatient mortality (p < 0.001). The data showed a progression in inpatient and 30-day mortality from AECOPD to PNA to PCOPD. Pneumonia and COPD differentially affected inpatient, 30-day and overall mortality with pneumonia affecting predominantly inpatient and 30-day mortality while COPD affecting the overall mortality.     

A prospective analysis of 184 hemoptysis cases: diagnostic impact of chest X-ray, computed tomography, bronchoscopy

BACKGROUND: The clinical presentation of hemoptysis often raises a number of diagnostic possibilities. OBJECTIVES: This study was designed to evaluate the relative frequency of different causes of hemoptysis and the value of chest radiography, computed tomography (CT) scanning and fiber-optic bronchoscopy in the evaluation of a Greek cohort population. METHODS: We prospectively followed a total of 184 consecutive patients (137 males/47 females, 145 smokers/39 nonsmokers) admitted with hemoptysis between January 2001 and December 2003 to the University Hospital of Heraklion. Follow-up data were collected on August 2005. RESULTS: The main causes of hemoptysis were bronchiectasis (26%), chronic bronchitis (23%), acute bronchitis (15%) and lung cancer (13%). Bronchiectasis was significantly more frequent in nonsmokers (p < 0.02). Among nonsmokers, patients with moderate/severe bleeding or a history of tuberculosis were more likely to have bronchiectasis (OR 8.25; 95% CI 1.9-35.9, p = 0.007 and OR 16.5; 95% CI 1.7-159.1, p = 0.007, respectively). Nonsmokers with normal or abnormal X-rays were equally likely to have bronchiectasis (OR 2.5; 95% CI 0.66-9.39, p = 0.2). Lung cancer was only found in smokers. Smokers with normal X-rays were less likely to have lung cancer compared to smokers with abnormal X-ray (OR 5.4; 95% CI 1.54-19.34, p = 0.004). There were no smokers with normal CT and lung cancer. Follow-up data were collected in 91% of patients. Lung cancer did not develop in any patient assumed to have hemoptysis of another origin than lung cancer on initial evaluation. CONCLUSIONS: Bronchiectasis is the main diagnosis in patients admitted with hemoptysis to a Greek University Hospital and it is more frequent among nonsmokers with moderate/severe bleeding and/or previous tuberculosis infection. Nonsmokers with moderate/severe hemoptysis and/or a history of tuberculosis should be evaluated with high-resolution CT. Smokers with hemoptysis are at increased risk for lung cancer and need to be extensively evaluated with chest CT and bronchoscopy.     

Polymorphisms in the Superoxide Dismutase-3 Gene Are Associated with Emphysema in COPD

ABSTRACT

Superoxide dismutase-3 (SOD3) is a major extracellular antioxidant enzyme, and previous studies have indicated a possible role of this gene in chronic obstructive pulmonary disease (COPD). We hypothesized that polymorphisms in the SOD3 gene would be associated with COPD and COPD-related phenotypes. We genotyped three SOD3 polymorphisms (rs8192287 (E1), rs8192288 (I1), and rs1799895 (R213G)) in a case–control cohort, with severe COPD cases from the National Emphysema Treatment Trial (NETT, n = 389) and smoking controls from the Normative Aging Study (NAS, n = 472). We examined whether the single nucleotide polymorphisms (SNPs) were associated with COPD status, lung function variables, and quantitative computed tomography (CT) measurements of emphysema and airway wall thickness. Furthermore, we tried to replicate our initial findings in two family-based studies, the International COPD Genetics Network (ICGN, n = 3061) and the Boston Early-Onset COPD Study (EOCOPD, n = 949). In NETT COPD cases, the minor alleles of SNPs E1 and I1 were associated with a higher percentage of emphysema (%LAA950) on chest CT scan (p = .029 and p = .0058). The association with E1 was replicated in the ICGN family study, where the minor allele was associated with more emphysema (p = .048). Airway wall thickness was positively associated with the E1 SNP in ICGN; however, this finding was not confirmed in NETT. Quantitative CT data were not available in EOCOPD. The SNPs were not associated with lung function variables or COPD status in any of the populations. In conclusion, polymorphisms in the SOD3 gene were associated with CT emphysema but not COPD susceptibility, highlighting the importance of phenotype definition in COPD genetics studies.     

Effect of Aclidinium Bromide on Exacerbations in Patients with Moderate-to-Severe COPD: A Pooled Analysis of Five Phase III,Randomized, Placebo-Controlled Studies

We investigated the effect of the long-acting muscarinic antagonist aclidinium bromide on chronic obstructive pulmonary disease (COPD) exacerbations by pooling data from five randomized, placebo-controlled, parallel-group Phase III studies of 3–6 months’ duration. Data were pooled from the aclidinium 400 μg twice-daily (BID) and placebo arms (N = 2,521) and stratified by Global initiative for chronic Obstructive Lung Disease (GOLD) group (A, B, C and D). Results showed that fewer patients experienced ≥1 exacerbation with aclidinium (any severity: 12.5%; moderate to severe: 10.9%) compared with placebo (any severity: 15.7%; moderate to severe: 13.3%) and the odds of experiencing ≥1 exacerbation of any severity were reduced in patients receiving aclidinium (odds ratio = 0.78, p = 0.039). Furthermore, aclidinium reduced the rate of exacerbations compared with placebo (any severity: rate ratio = 0.79, p = 0.026; moderate to severe: 0.80, p = 0.044). The time to first exacerbation of any severity was delayed with aclidinium compared with placebo (hazard ratio = 0.79, p = 0.026) and there was a numerical delay in time to first moderate-to-severe exacerbation. Finally, the effects of aclidinium on exacerbations versus placebo were greater in patients in GOLD Groups B and D; however, it is of note that only 10.7% of patients were classified in Group A or C. In summary, the results indicate that aclidinium 400 μg BID reduces the frequency of COPD exacerbations compared with placebo and that these effects are greater in symptomatic patients.     

Serum IgG and IgA antibodies to Chlamydia pneumoniae and severity of emphysema

OBJECTIVE: Chronic Chlamydia pneumoniae infection has been identified serologically in patients with COPD. The aim of this study was to examine whether the severity of emphysema is related to elevated antibody titres against C. pneumoniae. METHODOLOGY: We measured antibody titres against C. pneumoniae using ELISA, and assessed the severity of emphysema by the percentage of low attenuation area (%LAA) using high resolution (HR) CT in patients with COPD and in non-smoking control subjects. RESULTS: The mean %LAA was 2.2% in non-smoking controls (n = 28) and 13.3% in COPD patients (n = 94). COPD patients with a high IgG antibody index to C. pneumoniae (> or =2.0, n = 42) had a significantly higher %LAA (16.8%) than those with a low IgG index (<2.0, n = 52) (10.6%, P = 0.01). In addition, COPD patients with a high IgA antibody index (> or =2.0, n = 46) had a significantly higher %LAA (15.9%) than those with a low IgA index (<2.0, n = 48) (10.9%, P = 0.048). COPD patients with a high IgA antibody index also had a significantly lower %DLco than that associated with a low IgA index (68.1% and 80.3%, respectively, P = 0.007). There were no significant differences in age, smoking index or FEV(1)/FVC between these groups. CONCLUSION: These results suggest that high antibody titres against C. pneumoniae are linked with the severity of emphysema on high resolution CT and decreased diffusing capacity to carbon monoxide.