Rafael Vidal

Effect of exacerbations on quality of life in patients with chronic obstructive pulmonary disease: a 2 year follow up study

Background: A study was undertaken to evaluate exacerbations and their impact on the health related quality of life (HRQL) of patients with chronic obstructive pulmonary disease (COPD). Methods: A 2 year follow up study was performed in 336 patients with COPD of mean (SD) age 66 (8.2) years and mean (SD) forced expiratory volume in 1 second (FEV1) 33 (8)% predicted. Spirometric tests, questions regarding exacerbations of COPD, and HRQL measurements (St George’s Respiratory Questionnaire (SGRQ) and SF-12 Health Survey) were conducted at 6 month intervals. Results: A total of 1015 exacerbations were recorded, and 103 (30.7%) patients required at least one hospital admission during the study. After adjustment for baseline characteristics and season of assessment, frequent exacerbations had a negative effect on HRQL in patients with moderate COPD (FEV1 35–50% predicted); the change in SGRQ total score of moderate patients with ⩾3 exacerbations was almost two points per year greater (worse) than those with <3 exacerbations during the follow up (p = 0.042). For patients with severe COPD (FEV1 <35% predicted) exacerbations had no effect on HRQL. The change in SGRQ total score of patients admitted to hospital was almost 2 points per year greater (worse) than patients not admitted, but this effect failed to show statistical significance in any severity group. There was a significant and independent seasonal effect on HRQL since SGRQ total scores were, on average, 3 points better in measurements performed in spring/summer than in those measured in the winter (p<0.001). Conclusions: Frequent exacerbations significantly impair HRQL of patients with moderate COPD. A significant and independent effect of seasonality was also observed.

Diagnóstico y tratamiento de la tuberculosis

Lamentablemente, las novedades en tuberculosis (TB) se producen de forma lenta, demasiado lenta. No obstante, han pasado bastantes anos desde las ultimas Normativas de la Sociedad Espanola de Neumologia y Cirugia Toracica (SEPAR) sobre el diagnostico y el tratamiento de la TB, y durante este periodo no solo se han producido avances en el diagnostico y el tratamiento, especialmente en el campo del diagnostico, sino que ademas hemos asistido a un importante cambio demografico en Espana motivado por el incremento de la inmigracion. En la actualidad el 10% del total de la poblacion espanola no ha nacido en el pais y el 30% de los casos de TB corresponden a pacientes inmigrantes. Por todo ello, nos ha parecido oportuno y necesario revisar nuestras guias para actualizarlas y adaptarlas a la presente configuracion social espanola. En un esfuerzo de simplificacion hemos decidido agrupar en una sola las normativas previas sobre diagnostico y tratamiento de la TB. Para la elaboracion de la presente guia hemos tenido en cuenta la evidencia cientifica disponible. El grado de recomendacion se clasifica como A, B, C y D. El grado A significa que la evidencia cientifica en que se basa es buena o muy buena (estudios de nivel 1); el B, que es razonablemente buena (estudios de nivel 2); el C, que es escasa (series y casos), y el D, que asienta en opiniones de expertos y consensos. Agradecemos al Comite Cientifico de la SEPAR la deferencia y la confianza que han otorgado al grupo de expertos para llevar a cabo la nueva Normativa y esperamos y deseamos que sea de utilidad para mejorar el control de la TB. DIAGNOSTICO DE LA INFECCION TUBERCULOSA

Documento de consenso sobre diagnóstico, tratamiento y prevención de la tuberculosis

Pulmonary TB should be suspected in patients with respiratory symptoms longer than 2-3 weeks. Immunosuppression may modify clinical and radiological presentation. Chest X-ray shows very suggestive, albeit sometimes atypical, signs of TB. Complex radiological tests (CT scan, MR) are more useful in extrapulmonary TB. At least 3 serial representative samples of the clinical location are used for diagnosis whenever possible. Bacilloscopy and liquid medium cultures are indicated in all cases. Genetic amplification techniques are coadjuvant in moderate or high TB suspicion. Administration of isoniazid, rifampicin, ethambutol and pyrazinamide (HREZ) for 2 months and HR for 4 additional months is recommended in new cases of TB, except in cases of meningitis in which treatment should continue for up to 12 months and up to 9 months in spinal TB with neurological involvement, and in silicosis. Appropriate adjustments with antiretroviral treatment should be made in HIV patients. Combined therapy is recommended to avoid development of resistance. An antibiogram to first line drugs should be performed in all the initial isolations of new patients. Treatment control is one of the most important activities in TB management. The Tuberculin Skin Test (TST) is positive in TB infection when >or=5mm, and Interferon-Gamma Release Assays (IGRA) are recommended in combination with TT. The standard treatment schedule for infection is 6 months with isoniazid. In pulmonary TB, respiratory isolation is applied for 3 weeks or until 3 negative bacilloscopy samples are obtained.

Diagnóstico y tratamiento del déficit de alfa-1-antitripsina

Guidelines on Diagnosis and Treatment of Alpha-1 Antitrypsin Deficiency The alpha-1 antitrypsin (AAT) deficiency is a rare hereditary condition which is rarely diagnosed in the world, including Argentina. Underdiagnosis is mainly due to lack of Correspondencia: Guillermo Menga Domicilio postal: Finochietto 849 (CP 1272)CABAArg Tel.: 4307-6738 E-mail: mengagaamr@gmail.com Recibido: 12.01.2014 Aceptado: 14.02.2014 RAMR 2014;1:28-46

Simple method for α1-antitrypsin deficiency screening by use of dried blood spot specimens

The use of dried blood spot (DBS) specimens in quantitative alpha1-antitrypsin (alpha1-AT) detection or genetic analysis is limited because protein levels in the samples are low and they contain components that can interfere with polymerase chain reaction amplification. A methodological adaptation was developed to overcome these drawbacks which is discussed here. The study population consisted of 200 healthy volunteers and 300 patients with chronic obstructive pulmonary disease (COPD). DBS specimens were tested for alpha1-AT concentration using a modified nephelometric assay and phenotyped with an isoelectric focusing method. Genetic diagnosis was established by deoxyribonucleic acid sequencing using a simple purification procedure to remove contaminants. The nephelometric method showed a detection limit of 0.284 mg x dL(-1), corresponding to a serum concentration of 13 mg x dL(-1). The correlation coefficient between alpha1-AT concentrations in DBS versus serum samples was R2=0.8674 (p<0.0001). All 200 healthy individuals had DBS alpha1-AT concentrations >1.9 mg x dL(-1), corresponding to 114 mg x dL(-1) in serum samples. One hundred and twenty-five COPD patients (42%) showed alpha1-AT values <1.8 mg x dL(-1). Twenty patients with the PIZ phenotype had alpha1-AT values lower than 0.64 mg x dL(-1). On the basis of genotyping, one COPD patient was classified as heterozygous (PIMM(heerlen)). Selective elution of contaminants resulted in optimal alpha(1)1-antitrypsin genotyping. Because of its sensitivity and excellent correlation with the standard method, the dried blood spot quantitative assay is a reliable tool for routine measurement of alpha1-antitrypsin.

Tuberculosis treatment adherence and fatality in Spain.

BackgroundThe adherence to long tuberculosis (TB) treatment is a key factor in TB control programs. Always some patients abandon the treatment or die. The objective of this study is to identify factors associated with defaulting from or dying during antituberculosis treatment.MethodsProspective study of a large cohort of TB cases diagnosed during 2006-2007 by 61 members of the Spanish Society of Pneumology and Thoracic Surgery (SEPAR). Predictive factors of completion outcome (cured plus completed treatment vs. defaulters plus lost to follow-up) and fatality (died vs. the rest of patients) were based on logistic regression, calculating odds ratios (OR) and 95% confidence intervals (CI).ResultsOf the 1490 patients included, 29.7% were foreign-born. The treatment outcomes were: cured 792 (53.2%), completed treatment 540 (36.2%), failure 2 (0.1%), transfer-out 33 (2.2%), default 27 (1.8%), death 27 (1.8%), lost to follow-up 65 (4.4%), other 4 (0.3%). Completion outcome reached 93.5% and poor adherence was associated with: being an immigrant (OR = 2.03; CI:1.06-3.88), living alone (OR = 2.35; CI:1.05-5.26), residents of confined institutions (OR = 4.79; CI:1.74-13.14), previous treatment (OR = 2.93; CI:1.44-5.98), being an injecting drug user (IDU) (OR = 9.51; CI:2.70-33.47) and treatment comprehension difficulties (OR = 2.93; CI:1.44-5.98). Case fatality was 1.8% and it was associated with the following variables: age 50 or over (OR = 10.88; CI:1.12-105.01), retired (OR = 12.26;CI:1.74-86.04), HIV-infected (OR = 9.93; CI:1.48-66.34), comprehension difficulties (OR = 4.07; CI:1.24-13.29), IDU (OR = 23.59; CI:2.46-225.99) and Directly Observed Therapy (DOT) (OR = 3.54; CI:1.07-11.77).ConclusionImmigrants, those living alone, residents of confined institutions, patients treated previously, those with treatment comprehension difficulties, and IDU patients have poor adherence and should be targeted for DOT. To reduce fatality rates, stricter monitoring is required for patients who are retired, HIV-infected, IDU, and those with treatment comprehension difficulties.

Treatment and quality of life in patients with chronic obstructive pulmonary disease

Treatments administered to patients with chronic obstructive pulmonary disease (COPD), especially when used in multiple combinations, are not free of interactions and side effects that can potentially impair health-related quality of life (HRQL). We studied HRQL and its relationship with treatment in a group of 441 patients with stage II or III COPD (age: 66.6 (SD: 8.3) years; FEV1: 32.4% (SD: 8.1%)) using the St Georges Respiratory Questionnaire (SGRQ) and the 12-item short form (SF-12) Health Survey. The most prescribed drugs were ipratropium bromide (87.5%), inhaled corticosteroids (69.4%) and short-acting β-2 agonists (64.9%). Patients with stage III of the disease were receiving more drugs, particularly short-acting β-2 agonists (p = 0.002) and inhaled corticosteroids (p = 0.031). The use of theophyllines was associated with a worse total SGRQ score (β = 4.49; p < 0.001), although this negative association decreased with advanced age. A trend towards worse SGRQ scores was observed with the use of high doses of long-acting β-2 agonists (β = 3.22; p = 0.072). Patients receiving three drugs or more presented worse total SGRQ scores than patients receiving fewer drugs (β = 6.1, p < 0.001; and β = 7.64, p < 0.001, respectively). These findings suggest that the use of multiple drugs in the treatment of patients with COPD is associated with worse total SGRQ scores. The effect of drugs, their dosages and associations with other drugs on HRQL merit further research.

Usefulness of a national registry of alpha-1-antitrypsin deficiency. The Spanish experience☆

Severe alpha-1-antitrypsin (AAT) deficiency, phenotype Pi ZZ, is a rare condition with an estimated prevalence of 1/4500 individuals in Spain. Given this low prevalence, it seems useful to accumulate all the information derived from the care of these patients. In this context, the Spanish Registry of patients with AAT deficiency was founded in 1993; its main objectives were to establish guidelines adapted to our country for the treatment and management of AAT-deficient patients, offer expert support to physicians all over the country treating these patients, and provide technical support on the determination of Pi phenotyping and genotyping of individuals suspected of being AAT-deficient. From 1993 to January 1998 the number of enrollees increased from 48 to 223, of which 216 were Pi ZZ. Seventy-three per cent were male and only 31.5% were never smokers, mean age was 46 years (SD = 13 years) and mean FEV1 53% predicted (SD = 31%). 83% were index cases who, compared with non-index cases, were older (49 +/- 11 vs. 35 +/- 13 years, P < 0.001), more likely to have a smoking history (85% vs. 47%, P < 0.01) and displayed more severe impairment in pulmonary function (FEV1% = 40% +/- 19% vs. 96% +/- 23%, P < 0.001). Augmentation therapy was administered to 129 patients (58%). Treated patients had more severe impairment in pulmonary function than the untreated (FEV1% = 40% +/- 21% vs. 72% +/- 32%, P < 0.001) and were more likely to be index cases (81% vs. 43%, P < 0.001). Characteristics of the patients included are similar to those described for other Registries. The Registry has extended knowledge of the disease throughout the country and has established local guidelines for treatment and follow-up. It may be a valid database for future co-operation in international initiatives.

Results of a case-detection programme for α1-antitrypsin deficiency in COPD patients

α1-Antitrypsin (α1-AT) deficiency is an underdiagnosed condition in patients with chronic obstructive pulmonary disease (COPD). The present authors have conducted a nationwide case detection programme of α1-AT deficiency in unselected patients with COPD using dried blood spots. The first phase analysed samples from 971 patients by determining α1-AT concentrations and identifying the deficient Z allele by genotyping using rapid real-time PCR. The second phase analysed 1,166 samples with α1-AT concentrations and identified both the S and the Z allele, but only in samples with low α1-AT concentrations. A total of eight (0.37%) individuals with the severe deficiency PiZZ were detected. In addition, three patients were identified with the PiSZ genotype in the second phase (0.3%). The global cost of the programme was \#8364;41,512, which represents \#8364;19.42 per sample and \#8364;5,189 per PiZZ detected. A sensitivity analysis demonstrated that performing Z genotype to all samples would have resulted in increased costs of \#8364;28 per sample and \#8364;7,479.5 per PiZZ case identified. In conclusion, a case detection programme of α1-antitrypsin deficiency in patients with chronic obstructive pulmonary disease using dried blood spots is feasible and at a reasonable cost per case detected. Diagnostic yield and costs depend largely on inclusion criteria and the protocol for processing of samples.

[Consensus document on the diagnosis, treatment and prevention of tuberculosis].

Abstract Pulmonary tuberculosis must be suspected in patients with respiratory symptoms longer than 2–3 weeks. Immunosuppression may modify the clinical and radiological presentation. The chest X-ray is highly suggestive of tuberculosis (TB), but is occasionally atypical. The complex radiological tests (CT scan, MRI) are more useful in extrapulmonary TB. At least 3 consecutive representative samples from the clinical location are used for diagnosis, whenever possible. Bacilloscopy and liquid medium cultures are indicated in all cases. Genetic amplification techniques are coadjuvant in moderate or high suspicion of TB. In new cases of TB, administration of isoniazid, rifampin, ethambutol, and pyrazinamide (HREZ) for 2 months and isoniazid plus rifampin for 4 months is recommended. For meningitis cases, treatment should continue for up to 12 months, and up to 9 months in spinal TB with neurological affectation and silicosis. Appropriate adjustments with antiretroviral treatment must be made in HIV patients. Combined therapy is recommended to prevent development of resistance. An antibiogram for first line drugs should be performed in all initial extractions from new patients. Treatment control is one of the most important activities in TB management. The Tuberculin Skin Test (TST) is positive in TB infection when ≥ 5mm, and Interferon-Gamma Release Assays (IGRA) are recommended in combination with TST. The standard treatment schedule for infection is 6 months with isoniazid. In pulmonary TB, respiratory isolation is applied for 3 weeks or until 3 negative bacilloscopy samples are obtained.