Clinical impact of chronic obstructive pulmonary disease on non-cystic fibrosis bronchiectasis. A study on 1,790 patients from the Spanish Bronchiectasis Historical Registry.

BACKGROUND: Few studies have evaluated the coexistence of bronchiectasis (BE) and chronic obstructive pulmonary disease (COPD) in series of patients diagnosed primarily with BE. The aim of this study was to analyse the characteristics of patients with BE associated with COPD included in the Spanish Bronchiectasis Historical Registry and compare them to the remaining patients with non-cystic fibrosis BE. METHODS: We conducted a multicentre observational study of historical cohorts, analysing the characteristics of 1,790 patients who had been included in the registry between 2002 and 2011. Of these, 158 (8.8%) were registered as BE related to COPD and were compared to the remaining patients with BE of other aetiologies. RESULTS: Patients with COPD were mostly male, older, had a poorer respiratory function and more frequent exacerbations. There were no differences in the proportion of patients with chronic bronchial colonisation or in the isolated microorganisms. A significantly larger proportion of patients with COPD received treatment with bronchodilators, inhaled steroids and intravenous antibiotics, but there was no difference in the use of long term oral or inhaled antibiotherapy. During a follow-up period of 3.36 years, the overall proportion of deaths was 13.8%. When compared to the remaining aetiologies, patients with BE associated with COPD presented the highest mortality rate. The multivariate analysis showed that the diagnosis of COPD in a patient with BE as a primary diagnosis increased the risk of death by 1.77. CONCLUSION: Patients with BE related to COPD have the same microbiological characteristics as patients with BE due to other aetiologies. They receive treatment with long term oral and inhaled antibiotics aimed at controlling chronic bronchial colonisation, even though the current COPD treatment guidelines do not envisage this type of therapy. These patients' mortality is notably higher than that of remaining patients with non-cystic fibrosis BE.

Sex bias in diagnostic delay in bronchiectasis: An analysis of the Spanish Historical Registry of Bronchiectasis.

Diagnostic delay is common in most respiratory diseases, particularly in bronchiectasis. However, sex bias in diagnostic delay has not been studied to date. OBJECTIVE: Assessment of diagnostic delay in bronchiectasis by sex. METHODS: The Spanish Historical Registry of Bronchiectasis recruited adults diagnosed with bronchiectasis from 2002 to 2011 in 36 centres in Spain. From a total of 2113 patients registered we studied 2099, of whom 1125 (53.6%) were women. RESULTS: No differences were found for sex or age (61.0 ± 20.6, p = 0.88) or for localization of bronchiectasis ( p = 0.31). Bronchiectasis of unknown aetiology and secondary to asthma, childhood infections and tuberculosis was more common in women (all ps < 0.05). More men than women were chronic obstructive pulmonary disease-related bronchiectasis and colonized by Haemophilus influenzae ( p < 0.001 for both). Onset of symptoms was earlier in women. The diagnostic delay for women with bronchiectasis was 2.1 years more than for men ( p = 0.001). DISCUSSION: We recorded a substantial delay in the diagnosis of bronchiectasis. This delay was significantly longer in women than in men (>2 years). Independent factors associated with this sex bias were age at onset of symptoms, smoking history, daily expectoration and reduced lung function.

Etiology of Bronchiectasis in a Cohort of 2047 Patients. An Analysis of the Spanish Historical Bronchiectasis Registry. / Etiología de las bronquiectasias en una cohorte de 2.047 pacientes. Análisis del registro histórico español.

INTRODUCTION: Bronchiectasis is caused by many diseases. Establishing its etiology is important for clinical and prognostic reasons. The aim of this study was to evaluate the etiology of bronchiectasis in a large patient sample and its possible relationship with demographic, clinical or severity factors, and to analyze differences between idiopathic disease, post-infectious disease, and disease caused by other factors. METHODS: Multicenter, cross-sectional study of the SEPAR Spanish Historical Registry (RHEBQ-SEPAR). Adult patients with bronchiectasis followed by pulmonologists were included prospectively. Etiological studies were based on guidelines and standardized diagnostic tests included in the register, which were later included in the SEPAR guidelines on bronchiectasis. RESULTS: A total of 2,047 patients from 36 Spanish hospitals were analyzed. Mean age was 64.9years and 54.9% were women. Etiology was identified in 75.8% of cases (post-Infection: 30%; cystic fibrosis: 12.5%; immunodeficiencies: 9.4%; COPD: 7.8%; asthma: 5.4%; ciliary dyskinesia: 2.9%, and systemic diseases: 1.4%). The different etiologies presented different demographic, clinical, and microbiological factors. Post-infectious bronchiectasis and bronchiectasis caused by COPD and asthma were associated with an increased risk of poorer lung function. Patients with post-infectious bronchiectasis were older and were diagnosed later. Idiopathic bronchiectasis was more common in female non-smokers and was associated with better lung function, a higher body mass index, and a lower rate of Pseudomonas aeruginosa than bronchiectasis of known etiology. CONCLUSIONS: The etiology of bronchiectasis was identified in a large proportion of patients included in the RHEBQ-SEPAR registry. Different phenotypes associated with different causes could be identified.

Age-related risk factors for bacterial aetiology in community-acquired pneumonia.

BACKGROUND AND OBJECTIVE: The objective of this study was to evaluate the effect of age and comorbidities, smoking and alcohol use on microorganisms in patients with community-acquired pneumonia (CAP). METHODS: A prospective multicentre study was performed with 4304 patients. We compared microbiological results, bacterial aetiology, smoking, alcohol abuse and comorbidities in three age groups: young adults (<45 years), adults (45-64 years) and seniors (>65 years). RESULTS: Bacterial aetiology was identified in 1522 (35.4%) patients. In seniors, liver disease was independently associated with Gram-negative bacteria (Haemophilus influenzae and Enterobacteriaceae), COPD with Pseudomonas aeruginosa (OR = 2.69 (1.46-4.97)) and Staphylococcus aureus (OR = 2.8 (1.24-6.3)) and neurological diseases with S. aureus. In adults, diabetes mellitus (DM) was a risk factor for Streptococcus pneumoniae and S. aureus, and COPD for H. influenzae (OR = 3.39 (1.06-10.83)). In young adults, DM was associated with S. aureus. Smoking was a risk factor for Legionella pneumophila regardless of age. Alcohol intake was associated with mixed aetiology and Coxiella burnetii in seniors, and with S. pneumoniae in young adults. CONCLUSION: It should be considered that the bacterial aetiology may differ according to the patient's age, comorbidities, smoking and alcohol abuse. More extensive microbiological testing is warranted in those with risk factors for infrequent microorganisms.

Addiction and Other Reasons Adolescent Smokers Give to Justify Smoking.

BACKGROUND: The primary purpose of this paper is to examine youth addiction and other justifications for adolescent smoking, and how they affect the level of consumption. METHODS: Data from the Spanish 'State Survey on Drug Use among High School Students' aged between 14 and 18 years old were used in this paper. To account for the nature of the cigarette consumption data, several count data models were estimated in order to select the one that best fits adolescent smoking consumption. RESULTS: Most adolescent smokers smoke because it relaxes them, and about a quarter of them recognize that they are addicted. Moreover, the latter group smoke 44% more cigarettes than the rest (IRR = 1.444), revealing the strong addictive nature of tobacco, even at early ages. Moreover, parents' smoking increases the probability of smoking and has an impact on the level of consumption. CONCLUSIONS: The implications of these findings offer insight for parents, researchers, educators, and cessation interventionists, as awareness of self-reported and other predictors held by smoking youth creates a vantage point to facilitate changes in smoking behavior.

Tobacco smoking increases the risk for death from pneumococcal pneumonia.

BACKGROUND: Active smoking increases the risk of developing community-acquired pneumonia (CAP) and invasive pneumococcal disease, although its impact on mortality in pneumococcal CAP outcomes remains unclear. The aim of this study was to investigate the influence of current smoking status on pneumococcal CAP mortality. METHODS: We performed a multicenter, prospective, observational cohort study in 4,288 hospitalized patients with CAP. The study group consisted of 892 patients with pneumococcal CAP: 204 current smokers (22.8%), 387 nonsmokers (43.4%), and 301 exsmokers (33.7%). RESULTS: Mortality at 30 days was 3.9%: 4.9% in current smokers vs 4.3% in nonsmokers and 2.6% in exsmokers. Current smokers with CAP were younger (51 years vs 74 years), with more alcohol abuse and fewer cardiac, renal, and asthma diseases. Current smokers had lower CURB-65 (confusion, uremia, respiratory rate, BP, age ≥ 65 years) scores, although 40% had severe sepsis at diagnosis. Current smoking was an independent risk factor (OR, 5.0; 95% CI, 1.8-13.5; P = .001) for 30-day mortality of pneumococcal CAP after adjusting for age (OR, 1.06; P = .001), liver disease (OR, 4.5), sepsis (OR, 2.3), antibiotic adherence to guidelines, and first antibiotic dose given < 6 h. The independent risk effect of current smokers remained when compared only with nonsmokers (OR, 4.0; 95% CI, 1.3-12.6; P = .015) or to exsmokers (OR, 3.9; 95% CI, 1.09-4.95; P = .02). CONCLUSIONS: Current smokers with pneumococcal CAP often develop severe sepsis and require hospitalization at a younger age, despite fewer comorbid conditions. Smoking increases the risk of 30-day mortality independently of tobacco-related comorbidity, age, and comorbid conditions. Current smokers should be actively targeted for preventive strategies.

Variants at the promoter of the interleukin-6 gene are associated with severity and outcome of pneumococcal community-acquired pneumonia.

PURPOSE: Conflicting results about the role of genetic variability at IL6, particularly the -174 G/C single nucleotide polymorphism (SNP), in sepsis have been reported. We studied the genetic variability at IL6 in patients with community-acquired pneumonia (CAP) and pneumococcal CAP (P-CAP). METHODS: This was a multicenter, prospective observational study. IL6 -174 was analyzed in 1,227 white Spanish patients with CAP (306 with P-CAP). IL6 1753 C/G (N = 750), 2954 G/C (N = 845), and haplotypes defined by these SNPs were also studied. RESULTS: In CAP patients the genotype -174 GG were associated with protection against acute respiratory distress syndrome (ARDS) (p = 0.008, OR = 0.4, 95% CI 0.2-0.8). No other significant associations were observed. However, in patients with P-CAP multivariate analysis adjusted for age, gender, co-morbidity, hospital of origin, and severity (pneumonia severity index, PSI) showed that the IL6 -174 GG genotype was protective against the development of ARDS (p = 0.002, OR = 0.25, 95% CI 0.07-0.79), septic shock (p = 0.006, OR = 0.46, 95% CI 0.18-0.79), and multiple organ dysfunction syndrome (p = 0.02, OR = 0.53, 95% CI 0.27-0.89). P-CAP patients homozygous for IL6 -174 G also showed a higher survival in a logistic regression analysis adjusted for age, gender, co-morbidity, hospital of origin, and PSI (p = 0.048, OR = 0.27, 95% CI 0.07-0.98). CONCLUSIONS: Our results indicate that the IL-6 -174 GG genotype is associated with lower severity and mortality in patients with P-CAP. This effect was higher than that observed in patients with CAP irrespective of the causal pathogen involved. Our results highlight the importance of the causal pathogen in genetic epidemiological studies in sepsis.

[Geographical variations in the prevalence of COPD in Spain: relationship to smoking, death rates and other determining factors]. / Diferencias geográficas en la prevalencia de EPOC en España: relación con hábito tabáquico, tasas de mortalidad y otros determinantes.

BACKGROUND: The EPI-SCAN study (Epidemiologic Study of COPD in Spain), conducted from May 2006 to July 2007, determined that the prevalence of COPD in Spain according to the GOLD criteria was 10.2% of the 40 to 80 years population. Little is known about the current geographical variation of COPD in Spain. OBJECTIVES: We studied the prevalence of COPD, its under-diagnosis and under-treatment, smoking and mortality in the eleven areas participating in EPI-SCAN. COPD was defined as a post-bronchodilator FEV1/FVC ratio <0.70 or as the lower limit of normal (LLN). RESULTS: The ratio of prevalences of COPD among the EPI-SCAN areas was 2.7-fold, with a peak in Asturias (16.9%) and a minimum in Burgos (6.2 %) (P<0.05). The prevalence of COPD according to LLN was 5.6% (95% CI 4.9-6.4) and the ratio of COPD prevalence using LLN was 3.1-fold, but with a peak in Madrid-La Princesa (10.1%) and a minimum in Burgos (3.2%) (P<0.05). The ranking of prevalences of COPD was not maintained in both sexes or age groups in each area. Variations in under-diagnosis (58.6% to 72.8%) and under-treatment by areas (24.1% to 72.5%) were substantial (P<0.05). The prevalence of smokers and former smokers, and cumulative exposure as measured by pack-years, and the age structure of each of the areas did not explain much of the variability by geographic areas. Nor is there any relation with mortality rates published by Autonomous Communities. CONCLUSION: There are significant variations in the distribution of COPD in Spain, either in prevalence or in under-diagnosis and under-treatment.

[Starling-induced hypersensitivity pneumonitis: minimal but persistent antigen exposure]. / Neumonitis por hipersensibilidad crónica por estorninos. Exposición antigénica no masiva pero persistente.

A 51-year old woman developed hypersensitivity pneumonitis (HP) after inhaling the excrement of starlings that populated a park adjacent to her home. The clinical symptoms consisted of a non-productive cough and grade II dyspnea and radiological interstitial micronodular involvement. The respiratory function tests showed a restrictive pattern with desaturation on effort and a biopsy using videothorascopy was highly suggestive of HP. After taking a very detailed clinical history the patient mentioned an increase in cough when she crossed a park near her home, where a high population of starlings lived in its trees. Specific antigen extracts were prepared and skin tests were performed, precipitins measured, and bronchial provocation tests specific to this antigen were all positive. This observation identified a species of bird capable of causing the disease and shows a lung disease secondary to the exposure of a not very large but persistent antigen load.

Genetic variability in the severity and outcome of community-acquired pneumonia.

BACKGROUND: Several studies have investigated single nucleotide polymorphisms (SNP) in candidate genes associated with susceptibility, severity or outcome in patients with community-acquired pneumonia (CAP) with conflicting results. METHODS: Multi-centre, prospective observational study. We studied 1162 white Spanish patients with CAP and 1413 controls. Severe forms of sepsis were recorded in 325 patients. Subjects were genotyped for the following polymorphisms: TNF -238 and -308, LTA +252, IL6 -174, IL1RN 86bp variable number of tandem repeats and TNFRSF1B+676 (TNFR2 M196R). RESULTS: No significant differences in genotype or allele frequencies were seen among patients and controls. We did not find any association between TNF, LTA, IL6 and IL1RN polymorphisms with disease severity or outcome. Analysis of 28-day mortality showed a significant difference in the distribution of TNFRSF1B+676 G/T genotypes (p=0.0129). Sequential Kaplan-Meier survival analysis of TNFRSF1B+676 G/T polymorphism showed a protective role of the GT genotype. Cox regression analysis adjusted for age, gender, hospital of origin and comorbidities showed that patients with GT genotypes had lower mortality rates compared to patients with GG or TT genotypes (p=0.02; HR 0.53; 95% CI 0.31-0.90 for 90-day survival; p=0.01; HR 0.41; 95% CI 0.21-0.81 for 28-day survival and p=0.049; HR 0.48; 95% CI 0.23-0.997 for 15-day survival). CONCLUSIONS: Our study does not support a role for the controversial studied polymorphisms of the TNF, LTA, IL6 and IL1RN genes in the susceptibility or outcome of CAP. A protective role of heterozygosity for the functionally relevant TNFRSF1B+676 polymorphism in the outcome of CAP was observed.

Jaagsiekte sheep retrovirus is not detected in human lung adenocarcinomas expressing antigens related to the Gag polyprotein of betaretroviruses.

A proportion of human lung adenocarcinomas (hLACs) express an antigen related to the major capsid protein (CA) of Jaagsiekte sheep retrovirus (JSRV), a Betaretrovirus that causes a transmissible lung cancer in sheep. In this study, we have investigated whether JSRV or related betaretroviruses are expressed in hLACs. Results obtained indicate that JSRV is not associated with human lung adenocarcinomas. However, a proportion of hLACs reacted positively in immunohistochemistry with antibodies specific towards different domains of the JSRV Gag suggesting that a bona fide retrovirus antigen could be expressed in these tumours. Further studies will be necessary to ascertain whether the detection of antigens cross-reacting with betaretrovirus Gag antisera in some hLACs is due to expression of a human endogenous retrovirus or, more unlikely, of an uncharacterized exogenous retrovirus.