Short- and medium-term prognosis in patients hospitalized for COPD exacerbation: the CODEX index.

BACKGROUND: No valid tools exist for evaluating the prognosis in the short and medium term after hospital discharge of patients with COPD. Our hypothesis was that a new index based on the CODEX (comorbidity, obstruction, dyspnea, and previous severe exacerbations) index can accurately predict mortality, hospital readmission, and their combination for the period from 3 months to 1 year after discharge in patients hospitalized for COPD. METHODS: A multicenter study of patients hospitalized for COPD exacerbations was used to develop the CODEX index, and a different patient cohort was used for validation. Comorbidity was measured using the age-adjusted Charlson index, whereas dyspnea, obstruction, and severe exacerbations were calculated according to BODEX (BMI, airfl ow obstruction, dyspnea, and previous severe exacerbations) thresholds. Information about mortality and readmissions for COPD or other causes was collected at 3 and 12 months after hospital discharge. RESULTS: Two sets of 606 and 377 patients were included in the development and validation cohorts, respectively. The CODEX index was associated with mortality at 3 months ( P < .0001; hazard ratio [HR], 1.5; 95% CI, 1.2-1.8) and 1 year ( P < .0001; HR, 1.3; 95% CI, 1.2-1.5 ), hospital readmissions in the same periods, and their combination (all P < .0001). All CODEX C statistics were superior to those of the BODEX, DOSE (dyspnea, airfl ow obstruction, smoking status, and exacerbation frequency), and updated ADO (age, dyspnea, and airfl ow obstruction) indexes. CONCLUSIONS: The CODEX index was a useful predictor of survival and readmission at both 3 months and 1 year after hospital discharge for a COPD exacerbation, with a prognostic capacity superior to other previously published indexes.

Exhaled nitric oxide fraction as an add-on to ACQ-7 for not well controlled asthma detection.

BACKGROUND: The measurement of fractional nitric oxide concentration in exhaled breath (FeNO), a noninvasive indicator of airway inflammation, remains controversial as a tool to assess asthma control. Guidelines currently limit asthma control assessment to symptom and spirometry based appraisals such as the Asthma Control Questionnaire-7 (ACQ-7). We aimed at determining whether adding FeNO to ACQ-7 improves current asthma clinical control assessment, through enhanced detection of not well controlled asthma. METHODS: Asthmatic subjects, classified as not well controlled as per ACQ-7 on regular clinical practice, were included in a prospective, multicenter fashion, and had their maintenance treatment adjusted on visit 1. On follow-up (visit 2) four weeks later, the subjects were reevaluated as controlled or not well controlled using ACQ-7 versus a combination of FeNO and ACQ-7. RESULTS: Out of 381 subjects enrolled, 225 (59.1%) had not well controlled asthma on visit 2 as determined by ACQ-7, and 264 (69.3%) as per combined FeNO and ACQ-7. The combination of FeNO to ACQ-7 increased by 14.8% the detection of not well controlled asthma following maintenance therapy adjustment. CONCLUSIONS: The addition of FeNO to ACQ-7 increased the detectability of not well controlled asthma upon adjustment of maintenance therapy. Adding a measure of airway inflammation to usual symptom and spirometry based scores increases the efficacy of current asthma clinical control assessment.

Comorbidities and short-term prognosis in patients hospitalized for acute exacerbation of COPD: the EPOC en Servicios de medicina interna (ESMI) study.

BACKGROUND: Comorbidities are frequent in patients hospitalized for COPD exacerbation, but little is known about their relation with short-term mortality and hospital readmissions. Our hypothesis is that the frequency and type of comorbidities impair the prognosis within 12 weeks after discharge. METHODS: A longitudinal, observational, multicenter study of patients hospitalized for a COPD exacerbation with spirometric confirmation was performed. Comorbidity information was collected using the Charlson index and a questionnaire that included other common conditions not included in this index. Dyspnea, functional status, and previous hospitalization for COPD or other reasons among other variables were investigated. Information on mortality and readmissions for COPD or other causes was collected up to 3 months after discharge. RESULTS: We studied 606 patients, 594 men (89.9%), with a mean (SD) age of 72.6 (9.9) years and a postbronchodilator FEV1 of 43.2% (21.2). The mean Charlson index score was 3.1 (2.0). On admission, 63.4% of patients had arterial hypertension, 35.8% diabetes mellitus, 32.8% chronic heart failure, 20.8% ischemic heart disease, 19.3% anemia, and 34% dyslipemia. Twenty-seven patients (4.5%) died within 3 months. The Charlson index was an independent predictor of mortality (P < .003; OR,1.23; 95% CI, 1.07-1.40), even after adjustment for age, FEV1, and functional status measured with the Katz index. Comorbidity was also related with the need for hospitalization from the ED, length of stay, and hospital readmissions for COPD or other causes. CONCLUSIONS: Comorbidities are common in patients hospitalized for a COPD exacerbation, and they are related to short-term prognosis.

Physicians' knowledge of inhaler devices and inhalation techniques remains poor in Spain.

BACKGROUND: Studies in many countries in the 1990s revealed deficiencies in physicians' knowledge about inhalation therapy. In an attempt to remedy this situation, Spanish scientific societies implemented a variety of educational strategies. The objective of the present study was to assess changes in attitudes and knowledge about inhalers and inhalation techniques in a sizable sample of physicians. METHODS: An 11-question multiple choice test was developed and administered throughout Spain to practicing physicians from specialties that frequently prescribe inhaler devices. The survey collected demographic characteristics (four items), preferences (two items), and issues related to knowledge (three items) and education (two items) about devices and inhalation techniques. Completion of the questionnaire was voluntary, individual, and anonymous. RESULTS: A total of 1514 respondents completed the questionnaire. Dry powder inhalers (DPI) were preferred by 61.2% physicians, but only 46.1% identified "inhale deeply and forcefully" as the most significant step in the inhalation maneuver using these devices. Only 27.7% stated that they always checked the patient's inhalation technique when prescribing a new inhaler. A composite variable, general inhaled therapy knowledge, which pooled the correct answers related to knowledge, revealed that only 14.2% physicians had an adequate knowledge of inhaled therapy. Multivariate analysis showed that this knowledge was lowest among internal medicine and primary care physicians. CONCLUSIONS: Prescribers' knowledge of inhalers and inhalation techniques remains poor in Spain. The causes should be identified in further research to allow effective educational strategies to be developed. Specific educational policies should be addressed to general practitioners.

Acute exacerbation of chronic obstructive pulmonary disease in primary care setting in Spain: the EPOCAP study.

BACKGROUND: The present study was designed to describe the clinical profile of acute exacerbations of chronic obstructive pulmonary disease (COPD) and the treatment prescribed by primary care physicians (PCPs) in Spain. METHOD: An observational, multicenter and cross-sectional study was performed in patients diagnosed with acute exacerbation of COPD and treated by PCPs. Patients diagnosed with asthma, cystic fibrosis, significant bronchiectasis or pneumonia were not included in the study. RESULTS: A total of 329 general physicians recruited 1088 evaluable patients across the country. Mean age was 66.5+/-10.2 years; male : female ratio was 3 : 1. Spirometry was performed in 28.3% of the patients. The number of acute exacerbations in the last year was 3.3+/-2.5; 88.7% had increased expectoration, 87.5% increased dyspnea, 64.4% increased sputum purulence, and 43.5% fever. A total of 6.1% (n = 59) of patients were hospitalized due to exacerbation. The most frequently prescribed medications were antibiotics (84.5%, n = 919), mucolytic agents (72.5%, n = 789), inhaled corticosteroids (ICs) (71.3%, n = 776), and short-acting beta-adrenergic drugs (67.8%, n = 738). Oral corticosteroids were prescribed to 436 patients (40.1%). CONCLUSIONS: The clinical profile of acute exacerbations of COPD treated in a primary care setting in Spain was characterized by shortness of breath and increased sputum production. Patients were managed by PCP mainly in outpatient clinics with antibiotics, mucolytic agents, inhaled corticosteroids, oral corticosteroids and short-acting beta-adrenergic agents. The percentage of patients with confirmed diagnosis of COPD by pulmonary function tests was very low.

[Effect of AM3 on health-related quality of life in patients with chronic obstructive pulmonary disease belonging to risk groups]. / Efecto de AM3 en la calidad de vida de pacientes con enfermedad pulmonar obstructiva crónica en subgrupos de riesgo.

BACKGROUND AND OBJECTIVE: AM3 is an immunomodulator that significantly improves the quality of life of patients with chronic obstructive pulmonary disease (COPD). This study examined the effect of AM3 on the quality of life of patients in different risk groups and identified the factors associated with change in this variable. PATIENTS AND METHOD: This was a randomized, double-blind, placebo-controlled trial involving parallel groups of patients. The duration of the trial was 6 months. The study involved 253 patients with a mean (standard deviation) age of 67.7 (8.1) years and a mean forced expiratory volume in one second (FEV1) of 49.7% (10.2%). RESULTS: Only 121 patients (47.8%) suffered at least one exacerbation during the 6 months period. At the end of the study period, the improvement in St. George's Respiratory Questionnaire (SGRQ) score in those patients who suffered an exacerbation but who received AM3 was significantly greater than that experienced by similar placebo-treated patients (-8.10 compared to -2.5 units; p=0.034). Patients treated with inhaled corticoids also improved more with AM3 than with placebo (-9.17 compared to -4.44; p=0.035). In the 108 patients with an FEV1 of <50%, the improvements were not significantly different (-9.57 vs. -6.57; p=0.23). The factors influencing the change in SGRQ score were baseline SGRQ (p<0.001), exacerbations (p<0.008), an FEV1 of <50% (p<0.032) and treatment with AM3 (p<0.004). CONCLUSIONS: Among the patients who experienced exacerbations, treatment with AM3 helped prevent the deterioration of their quality of life. Along with AM3 treatment, the factors that independently influenced the change in SGRQ score were suffering from an exacerbation and poorer pulmonary function.

Efecto de AM3 en la calidad de vida de pacientes con enfermedad pulmonar obstructiva crónica en subgrupos de riesgo / Effect of AM3 on health-related quality of life in patients with chronic obstructive pulmonary disease belonging to risk groups

Fundamento y objetivo: El AM3 es un inmunomodulador que ha demostrado mejorar de forma significativa la calidad de vida en pacientes con enfermedad pulmonar obstructiva crónica (EPOC). En este estudio se analiza su efecto en la calidad de vida en subgrupos de riesgo y se identifican los factores asociados con el cambio en la calidad de vida en pacientes con EPOC. Pacientes y método: Se trata de un ensayo clínico aleatorizado, doble ciego, controlado con placebo y de grupos paralelos de 6 meses de duración. Incluyó a 253 pacientes con una edad media (desviación estándar) de 67,7 (8,1) años y una cifra media de volumen espiratorio forzado en el primer segundo (FEV1) del 49,7% (10,2%). Resultados: Tan sólo 121 pacientes (47,8%) presentaron al menos una agudización. La mejoría en el St. George's Respiratory Questionnaire (SGRQ) en los pacientes que experimentaron agudizaciones y que recibieron AM3 fue significativamente superior a la de los que recibieron placebo (­8,10 frente a ­2,5 unidades; p < 0,034). Los pacientes tratados con corticoides inhalados también mejoraron más con AM3 que con placebo (­9,17 frente a ­4,44; p < 0,035). En los 108 pacientes con FEV1 menor del 50% las diferencias no fueron estadísticamente significativas (­9,57 frente a ­6,57; p = 0,23). Los factores asociados al cambio en el SGRQ fueron el SGRQ inicial (p < 0,001), la presencia de agudizaciones (p < 0,008), un valor del FEV1 inferior al 50% (p < 0,032) y el tratamiento con AM3 (p < 0,004). Conclusiones: En pacientes que presentaron agudizaciones durante el seguimiento, el tratamiento con AM3 previno el deterioro de la calidad de vida. Junto al tratamiento con AM3, la puntuación basal del SGRQ, la presencia de agudizaciones y una peor función pulmonar fueron factores asociados de forma independiente al cambio en el SGRQ

Background and objective: AM3 is an immunomodulator that significantly improves the quality of life of patients with chronic obstructive pulmonary disease (COPD). This study examined the effect of AM3 on the quality of life of patients in different risk groups and identified the factors associated with change in this variable. Patients and method: This was a randomized, double-blind, placebo-controlled trial involving parallel groups of patients. The duration of the trial was 6 months. The study involved 253 patients with a mean (standard deviation) age of 67.7 (8.1) years and a mean forced expiratory volume in one second (FEV1) of 49.7% (10.2%). Results: Only 121 patients (47.8%) suffered at least one exacerbation during the 6 months period. At the end of the study period, the improvement in St. George's Respiratory Questionnaire (SGRQ) score in those patients who suffered an exacerbation but who received AM3 was significantly greater than that experienced by similar placebo-treated patients (­8.10 compared to ­2.5 units; p = 0.034). Patients treated with inhaled corticoids also improved more with AM3 than with placebo (­9.17 compared to ­4.44; p = 0.035). In the 108 patients with an FEV1 of < 50%, the improvements were not significantly different (­9.57 vs. ­6.57; p = 0.23). The factors influencing the change in SGRQ score were baseline SGRQ (p < 0.001), exacerbations (p < 0.008), an FEV1 of < 50% (p < 0.032) and treatment with AM3 (p < 0.004). Conclusions: Among the patients who experienced exacerbations, treatment with AM3 helped prevent the deterioration of their quality of life. Along with AM3 treatment, the factors that independently influenced the change in SGRQ score were suffering from an exacerbation and poorer pulmonary function

Bird fancier's lung: a series of 86 patients.

Bird fancier's lung (BFL) is one of the most common types of hypersensitivity pneumonitis. Nevertheless, the criteria for diagnosing this condition are not standardized. The current study is an in-depth investigation into the clinical characteristics of BFL in the largest series examined for this purpose by a single group, to our knowledge, taking into account the acute, subacute, or chronic clinical presentation. From 1977 to 2003, BFL was diagnosed in 86 patients using a homogeneous protocol. Data from the clinical history and physical examination were analyzed, as well as the results from the following complementary examinations: laboratory analyses, specific serum IgG antibodies determination, chest X-ray, chest computed tomography (CT), pulmonary function testing, immediate hypersensitivity skin testing, delayed cutaneous hypersensitivity testing, bronchofibroscopy with bronchoalveolar lavage (BAL) and/or transbronchial biopsy, bronchial challenge testing, and surgical lung biopsy. In addition, clinical and epidemiologic characteristics were determined in a control group of 60 pigeon breeders who did not meet the diagnostic criteria of BFL. Eighty-six patients (21 men and 65 women) with a mean age of 47 years were studied. Seven (8%) patients were younger than 15 years of age at the time of the diagnosis. In 3 cases, the disease was caused by exposure to feather-filled bedding. Nearly 1 in 5 patients was diagnosed in the chronic phase of the disease. The mean diagnostic delay was 1.6 years overall, and 3.2 years in patients diagnosed in the chronic phase of the disease. Among the 17% of patients with chronic disease, the mean interval from initiation of exposure to diagnosis was 16 years, a higher value than in the acute or subacute presentation forms. Dyspnea and cough were the most common clinical symptoms (98% and 82%, respectively), and nearly 25% had grade III or IV dyspnea at diagnosis. Only 18% of patients experienced chest tightness, a symptom classically considered to be frequent in this condition. Erythrocyte sedimentation rate was elevated (>30 mm/h) in 44% of patients. Urinary calcium was elevated in 20% of patients. Angiotensin-converting enzyme was not elevated in any of the patients in which it was measured. Lactate dehydrogenase increases were found in 51% of patients. Specific IgG antibodies to avian antigens were documented in 92% of BFL patients, but also in 87% of pigeon breeder controls. The most frequent radiologic finding was an interstitial pattern in 79% of patients. Common chest CT features were ground glass areas (68%) and a mosaic pattern (61%); areas of emphysema were found in 7/41 (17%) patients, 5 of whom had never smoked. Two patients had a CT pattern of pulmonary fibrosis indistinguishable from idiopathic pulmonary fibrosis. Immediate hypersensitivity skin testing with bird sera and pigeon bloom was positive in 78% and 100% of BFL patients, respectively, and in 64% and 88% of control pigeon breeders, respectively. Almost one-third of the patients (29%) presented an anergic response on delayed cutaneous hypersensitivity testing. Restrictive ventilatory impairment was the most frequent functional pattern (77%), although 9% and 4% showed a pure obstructive and mixed pattern, respectively. The carbon monoxide diffusing capacity was decreased (<80% of the predicted value) in 85% of cases. Forty-one percent of patients had PaO2 <60 mm Hg at diagnosis when blood gas analysis was performed. Lymphocytosis (>20% lymphocytes) was documented in 83% of patients who underwent BAL, with a similar frequency in the 3 presentation forms: 70% acute, 89% subacute, and 85% chronic. In addition, inversion of the CD4/CD8 ratio (<1) was observed in 62% of the patients, but 38% of cases showed a CD4 predominance. The characteristic triad of histopathologic findings in hypersensitivity pneumonitis was found in only 9% of patients undergoing transbronchial biopsy, but at least 1 of these findings was seen in 69%. Surgical lung biopsy was undertaken in 14/86 (16%) patients; the complete triad was observed in 50% and at least 1 finding in 100%. In 54/86 (63%) patients, the diagnosis was confirmed by bronchial challenge testing, a test with a sensitivity of 92% and specificity of 100%. BFL is a potentially severe disease that can progress to respiratory failure secondary to pulmonary fibrosis or chronic obstructive pulmonary disease, as a form of chronic occupational respiratory disease. Respiratory symptoms in exposed patients, including children and adults who have only 1 pet bird at home, should raise the suspicion of BFL. Diagnosis in the chronic phase is frequent, and the delay to diagnosis was greatest in these cases. Elevated urinary calcium, lactate dehydrogenase, and erythrocyte sedimentation rate in a bird fancier may constitute a combined marker for suspected BFL. Chest CT frequently discloses emphysema and a pattern of idiopathic pulmonary fibrosis in some patients. An anergic response on delayed cutaneous hypersensitivity testing is not infrequent. The presentation with respiratory failure and the predominance of CD4 T lymphocytes in some patients' BAL are both remarkable. Lymphocytosis on BAL also persists in the chronic phase of the disease. Bronchial challenge testing has a high diagnostic yield, and surgical lung biopsy is not needed to reach the final diagnosis in the vast majority of cases.

Geographic differences in clinical characteristics and management of COPD: the EPOCA study.

AIMS: Data on differences in clinical characteristics and management of COPD in different countries and settings are limited. We aimed to characterize the profile of patients with COPD in a number of countries and their treatment in order to evaluate adherence to recommendations of international guidelines. METHOD: This was an observational, international, cross-sectional study on patients with physician-diagnosed COPD. Demographic and clinical characteristics, risk factors, and treatment were collected by their physician via an internet web-based questionnaire developed for the study. RESULTS: A total of 77 investigators from 17 countries provided data on 833 patients. The countries with the highest number of patients included were: Argentina (128), Ecuador (134), Spain (162), and Hong Kong (153). Overall, 79.3% were men and 81% former smokers, with a mean FEV1 = 42.7%, ranging from 34.3% in Hong Kong to 58.8% in Ecuador. Patients reported a mean of 1.6 exacerbations the previous year, with this frequency being significantly and negatively correlated with FEV1 (%) (r = -0.256; p < 0.0001). Treatment with short-acting bronchodilators and theophyllines was more frequent in Ecuador and Hong Kong compared with Spain and Argentina, and in patients belonging to lower socioeconomic levels (p < 0.0001 for all comparisons). Inadequacy of treatment with inhaled corticosteroids and theophyllines was high, with significant differences among countries. CONCLUSIONS: Differences in the clinical characteristics and management of COPD were significant across countries. Adherence to international guidelines appears to be low. Efforts should be made to disseminate and adapt guidelines to the socioeconomic reality of different settings.

Costs of chronic bronchitis and COPD: a 1-year follow-up study.

OBJECTIVE: This study attempted to determine the total direct costs derived from the management of chronic bronchitis and COPD in an ambulatory setting through a prospective, 1-year, follow-up study. METHOD: A total of 1,510 patients with chronic bronchitis and COPD were recruited from 268 general practices located throughout Spain. Patients were followed up for 1 year. All direct medical costs incurred by the cohort and related to their respiratory disease were quantified. Costs were calculated for patients with confirmed COPD according to the degree of severity of airflow obstruction. RESULTS: The global mean direct yearly cost of chronic bronchitis and COPD was $1,876. The cost generated by patients with COPD was $1,760, but the cost of severe COPD ($2,911) was almost double that of mild COPD ($1,484). Hospitalization costs represented 43.8% of costs, drug acquisition costs were 40.8%, and clinic visits and diagnostic tests represented only 15.4% of costs. CONCLUSION: This is the first prospective follow-up study on a large cohort of patients with chronic bronchitis and COPD aimed at quantifying direct medical costs under usual clinical practice in the community. Costs of chronic bronchitis and COPD were almost twofold those reported for asthma. Patterns of COPD management in the community differ from those recommended in guidelines. COPD represents a great health-care burden in developed countries, and aging of the population and continuing smoking habits predict that it will continue to do so in the future.

Speed of recovery from acute exacerbations of chronic obstructive pulmonary disease after treatment with antimicrobials : results of a two-year study.

OBJECTIVE: We performed a multicentre study under a 2-year observational protocol that included data on time to recovery from acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) in patients receiving moxifloxacin and comparator antimicrobials. PATIENTS AND METHODS: Outpatients with moderate or severe COPD were recruited from respiratory clinics throughout Spain. Moxifloxacin was available in year 2, and was to be prescribed to 50% of patients in that period in a non-randomised allocation. Time to recovery was compared in successfully treated AE-COPD; cross-sectionally for all AE-COPD over 2 years, first AE-COPD and all AE-COPD in year 2, and longitudinally in patients receiving comparator antimicrobials for AE-COPD in year 1 and moxifloxacin in year 2. RESULTS: 614 AE-COPD were treated in 441 patients over 2 years (mean age 66.7 +/- 8.3 years, 98% males, mean forced expiratory volume in 1 second [FEV(1)] 35.9 +/- 8.8%). Mean time to recovery overall was 4.6 days (SD 3.3) with moxifloxacin 400 mg/day for 5 days, and 5.8 days (SD 4.6) with comparators (p < 0.01), which were most frequently amoxicillin/clavulanic acid 500/125mg/8h, clarithromycin 500mg/12h and cefuroxime axetil 500mg/12h for 7-10 days. Longitudinal analysis showed that 27 patients treated with moxifloxacin in the second year of the study recovered in a mean of 3.7 days (SD 3.1), and the same patients treated with comparator antimicrobials in year one recovered in a mean of 6.8 days (SD 4.6) [p = 0.02]. In contrast, in 66 patients treated with comparator antimicrobials in both years, mean time to recovery was 7.4 days (SD 7.3) in year one and 5.5 days (SD 3.5) in year two (p = 0.24). All subgroup analyses showed a statistically significant reduction of 18-25% in time to recovery with moxifloxacin compared with other antibiotics. CONCLUSIONS: Moxifloxacin significantly reduced time to recovery from AE-COPD in patients with moderate to severe disease by approximately 20% (>1 day) compared with other antimicrobials. Faster recovery should result in earlier return to work or normal activities, and to social and economic savings.

Pharmacoeconomic evaluation of acute exacerbations of chronic bronchitis and COPD.

BACKGROUND: Although exacerbations are the main cause of medical visits and hospitalizations of patients with chronic bronchitis and COPD, little information is available on the costs of their management. OBJECTIVE: This study attempted to determine the total direct costs derived from the management of exacerbations of chronic bronchitis and COPD in an ambulatory setting. METHOD: A total of 2,414 patients with exacerbated chronic bronchitis and COPD were recruited from 268 general practices located throughout Spain. Patients were followed up for 1 month. RESULTS: A total of 507 patients (21%) relapsed; of these, 161 patients (31.7%) required attention in emergency departments and 84 patients (16.5%) were admitted to the hospital. The total direct mean cost of all exacerbations was $159; patients who were hospitalized generated 58% of the total cost. Cost per failure was $477.50, and failures were responsible for an added mean cost of $100.30/exacerbation. Exacerbations of the 1,130 patients with COPD had a mean cost of $141. Sensitivity analysis showed that a 50% reduction in the failure rate (from 21 to 10.5%) would result in a total cost of exacerbation of $107 (33% reduction). CONCLUSION: Exacerbations of chronic bronchitis and COPD are costly, but the greatest part of costs derives from therapeutic failures, particularly those that end in hospitalization.