Association of SLC11A1 with tuberculosis and interactions with NOS2A and TLR2 in African-Americans and Caucasians.

SETTING: Host defense factors may influence the development of active tuberculosis (TB). OBJECTIVE: To test variants in solute carrier family 11A, member 1 (SLC11A1), for an association with TB. METHODS: A mixed case-control study of TB cases, relatives or close contact controls, consisting of 474 African-Americans (243 families) and 381 Caucasians (192 families), examined 13 SLC11A1 polymorphisms for association with pulmonary TB using generalized estimating equations adjusting for age and sex. RESULTS: Two associations were observed in Caucasians (rs3731863, P = 0.03, and rs17221959, P = 0.04) and one in African-Americans (rs3731865, P = 0.05). Multilocus analyses between polymorphisms in SLC11A1 and 11 TB candidate genes detected interactions between SLC11A1 and inducible nitric oxide synthase (NOS2A) in Caucasians (rs3731863 [SLC11A1] x rs8073782 [NOS2A], P = 0.009; rs3731863 [SLC11A1] x rs17722851 [NOS2A], P = 0.007) and toll-like receptor 2 (TLR2) in African-Americans (rs3731865 [SLC11A1] x rs1816702, P = 0.005). CONCLUSIONS: No association was detected with 5'(GT)(n) promoter polymorphism previously associated with lower SLC11A1 expression, rs17235409 (D543N), or rs17235416 (3' TGTG insertion/deletion polymorphism). SLC11A1 polymorphism rs3731865 was associated with TB in African-Americans, consistent with previous findings in West Africans. These results suggest that variants in SLC11A1 increase susceptibility to pulmonary TB and interact with other variants that differ by race.

CD3 expression distinguishes two gammadeltaT cell receptor subsets with different phenotype and effector function in tuberculous pleurisy.

Tuberculous pleurisy is a naturally occurring site of Mycobacterium tuberculosis (Mtb) infection. Herein, we describe the expression of activation, natural killer (NK) and cell migration markers, as well as effector functions from gammadeltaT cells in peripheral blood (PB) and pleural effusion (PE) from tuberculosis patients (TB). We observed a decreased percentage of circulating gammadeltaT from TB patients and differential expression of NK as well as of chemokine receptors on PB and PE. Two subsets of gammadeltaT cells were differentiated by the CD3/gammadeltaT cell receptor (gammadeltaTCR) complex. The gammadeltaTCR(low) subset had a higher CD3 to TCR ratio and was enriched in Vdelta2(+) cells, whereas most Vdelta1(+) cells belonged to the gammadeltaTCR(high) subset. In PB from TB, most gammadeltaTCR(high) were CD45RA(+)CCR7(-) and gammadeltaTCR(low) were CD45RA(+/-)CCR7(+)CXCR3(+). In the pleural space the proportion of CD45RA(-)CCR7(+)CXCR3(+) cells was higher. Neither spontaneous nor Mtb-induced interferon (IFN)-gamma production was observed in PB-gammadeltaT cells from TB; however, PE-gammadeltaT cells showed a strong response. Both PB- and PE-gammadelta T cells expressed surface CD107a upon stimulation with Mtb. Notably, PE-gammadeltaTCR(low) cells were the most potent effector cells. Thus, gammadeltaT cells from PB would acquire a further activated phenotype within the site of Mtb infection and exert full effector functions. As gammadeltaT cells produce IFN-gamma within the pleural space, they would be expected to play a beneficial role in tuberculous pleurisy by helping to maintain a T helper type 1 profile.

IL-10 down-regulates costimulatory molecules on Mycobacterium tuberculosis-pulsed macrophages and impairs the lytic activity of CD4 and CD8 CTL in tuberculosis patients.

Activation of T cells requires both TCR-specific ligation and costimulation through accessory molecules during T cell priming. IFNgamma is a key cytokine responsible for macrophage activation during Mycobacterium tuberculosis (Mtb) infection while IL-10 is associated with suppression of cell mediated immunity in intracellular infection. In this paper we evaluated the role of IFNgamma and IL-10 on the function of cytotoxic T cells (CTL) and on the modulation of costimulatory molecules in healthy controls and patients with active tuberculosis (TB). gamma-irradiated-Mtb (i-Mtb) induced IL-10 production from CD14(+) cells from TB patients. Moreover, CD3(+) T cells of patients with advanced disease also produced IL-10 after i-Mtb stimulation. In healthy donors, IL-10 decreased the lytic activity of CD4(+) and CD8(+) T cells whereas it increased gammadelta-mediated cytotoxicity. Furthermore, we found that the presence of IL-10 induced a loss of the alternative processing pathways of antigen presentation along with a down-regulation of the expression of costimulatory molecule expression on monocytes and macrophages from healthy individuals. Conversely, neutralization of endogenous IL-10 or addition of IFNgamma to either effector or target cells from TB patients induced a strong lytic activity mediated by CD8(+) CTL together with an up-regulation of CD54 and CD86 expression on target cells. Moreover, we observed that macrophages from TB patients could use alternative pathways for i-Mtb presentation. Taken together, our results demonstrate that the presence of IL-10 during Mtb infection might contribute to mycobacteria persistence inside host macrophages through a mechanism that involved inhibition of MHC-restricted cytotoxicity against infected macrophages.

Treatment and follow-up of HIV-negative multidrug-resistant tuberculosis patients in an infectious diseases reference hospital, Buenos Aires, Argentina.

SETTING: An Argentinean reference hospital specialising in infectious diseases. OBJECTIVE: To assess the outcomes of all human immunodeficiency virus (HIV) negative multidrug-resistant tuberculosis (MDR-TB) patients referred to or diagnosed at Hospital Muñiz. DESIGN: Clinical study for the period 1996-1999, with follow-up until June 2002. RESULTS: One hundred and forty-one adult patients (52.5% female) with resistance to two to seven drugs were studied. Fifty patients (35.5%) had not been treated previously. The most frequently used second-line drugs were 5-F-quinolones, cycloserine and ethionamide in susceptibility based individually tailored three- to five-drug regimens. Hospital admission was associated with treatment success. Forty-five episodes of severe toxicity occurred. Treatment was successful in 51.8% of cases, but follow-up of 73 patients yielded 11.9% relapse. The mortality rate was 19.1% and default was 19.9%. Logistic regression analysis was statistically significant for treatment success in relation to patient admission, residence and resistance pattern. CONCLUSION: The burden of MDR-TB in this setting--prolonged infection, treatment cost and difficulties, low rates of cure and treatment adherence and high rates of fatality and relapse--can be improved by strengthening TB control programme activities and fighting against poverty and HIV/AIDS.

Monocytes and neutrophils from tuberculosis patients are insensitive to anti-inflammatory effects triggered by the prototypic formyl peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP).

Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis where formyl peptides, which are cleavage products of bacterial and mitochondrial proteins, are present. In this study, we demonstrated that interferon gamma (IFN)-gamma and interleukin (IL)-10 induced the overexpression of the receptor for the Fc portion of IgG I (FcgammaRI) in monocytes from tuberculosis (TB) patients, showing that these cells respond to IFN-gamma and IL-10 signals. We also demonstrated that lower doses of IL-10 render monocytes from TB patients less responsive to higher doses of the cytokine. Although the prototypic formyl peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) is a well-known proinflammatory agonist, we have demonstrated previously that preincubation of monocytes with FMLP inhibited the up-regulation of FcgammaRI induced by IFN-gamma or IL-10. This effect was not observed in monocytes from TB patients. FMLP also induced the down-regulation of the expression of FcgammaRI in monocytes that had been activated already with IFN-gamma. However, this effect of FMLP was not observed in monocytes from TB patients and supernatants from monocytes obtained from these patients were incapable of inducing the down-regulation of FcgammaRI. In contrast to normal donors, supernatants from FMLP-treated neutrophils from TB patients did not modify the basal level of expression of FcgammaRI in monocytes from normal donors. In conclusion, in this study we demonstrated the existence of two novel mechanisms that may contribute to the pathological effects generated by M. tuberculosis: the enhancement of FcgammaRI in response to IFN-gamma and IL-10, and the unresponsiveness to the anti-inflammatory effects induced by formyl peptides.

Specific lytic activity against mycobacterial antigens is inversely correlated with the severity of tuberculosis.

The ability of peripheral blood mononuclear cells (PBMC) from patients with active tuberculosis to display cytotoxic responses against autologous Mycobacterium tuberculosis (Mtb)-pulsed macrophages was evaluated. Non-MHC restricted cell-dependent lytic activity was observed in ex vivo effector cells from tuberculosis patients and was mediated mainly by CD3(+)gammadelta TCR(+) T (gammadelta T) cells bearing CD56 and/or CD16 molecules. MHC-restricted and non-MHC restricted cytotoxic T cells (CTL) were differentially expanded upon stimulation with Mtb in tuberculosis patients and normal controls (N). Class-I restricted CD8(+) CTL and class-II restricted CD4(+) CTL were generated in PPD(+)N and to a lesser extent in PPD(-)N. Mtb-stimulated effector cells from tuberculosis patients became progressively non-MHC restricted CD4(-)CD8(-)gammadelta T cells, while lytic activity of CD4(+) and CD8(+)CTL decreased gradually as the disease became more severe. On the other hand, target cells were lysed by ex vivo cells from tuberculosis patients through the Fas-FasL and perforin pathways. Mtb-induced CD4(+) CTL from tuberculosis patients and N controls preferentially employed the Fas-FasL mechanism. Mtb-induced CD8(+) CTL effector cells from patients used the perforin-based mechanism while cells from N controls also used the Fas-FasL pathway. While Mtb-induced gammadelta CTL from patients and PPD(-)N employed the latter mechanism cells from PPD(+)N individuals also used the perforin pathway. It can be concluded that shifts in the CTL response and the cytolytic mechanisms take place as the pulmonary involvement becomes more severe.

Activation of peripheral blood neutrophils from patients with active advanced tuberculosis.

Activation of peripheral blood neutrophils (PMN) was investigated in order to determine whether they might contribute to the inflammatory process during active advanced tuberculosis. Receptors for the Fc portion of IgG (FcgammaR) (FcgammaRI, FcgammaRII, and FcgammaRIIIB), CD66 (degranulation marker), and receptors for tumor necrosis factor-alpha (TNF-R55 and TNF-R75) were analyzed on PMN obtained from normal controls and tuberculosis patients (TB-PMN). Functional parameters such as cytotoxicity, superoxide anion generation triggered by N-formyl-methionyl-leucyl-phenyl-alanine (FMLP), and TNF-alpha and IL-1beta production were evaluated. A high expression of TNF-R55, CD66, and FcgammaRIIIB and the appearance of FcgammaRI were detected in TB-PMN. In addition, cytotoxicity, superoxide anion release, and TNF-alpha and IL-1beta production were enhanced in TB-PMN. Thus, in tuberculosis, the activation of PMN outside the focus of infection strongly suggests the possibility of a systemic inflammation that could modulate the inflammatory response.

Redox chemistry in laccase-catalyzed oxidation of N-hydroxy compounds.

1-Hydroxybenzotriazole, violuric acid, and N-hydroxyacetanilide are three N-OH compounds capable of mediating a range of laccase-catalyzed biotransformations, such as paper pulp delignification and degradation of polycyclic hydrocarbons. The mechanism of their enzymatic oxidation was studied with seven fungal laccases. The oxidation had a bell-shaped pH-activity profile with an optimal pH ranging from 4 to 7. The oxidation rate was found to be dependent on the redox potential difference between the N-OH substrate and laccase. A laccase with a higher redox potential or an N-OH compound with a lower redox potential tended to have a higher oxidation rate. Similar to the enzymatic oxidation of phenols, phenoxazines, phenothiazines, and other redox-active compounds, an "outer-sphere" type of single-electron transfer from the substrate to laccase and proton release are speculated to be involved in the rate-limiting step for N-OH oxidation.

Phase II trial of recombinant interferon-alpha2b in patients with advanced intractable multidrug-resistant pulmonary tuberculosis: long-term follow-up.

SETTING: Multidrug-resistant tuberculosis patients without human immunodeficiency virus (HIV) infection, with Mycobacterium tuberculosis resistant to almost all of the available drugs. OBJECTIVE: Limited phase II trial with recombinant interferon-alpha2b in five chronic multidrug-resistant tuberculosis patients. METHODS: Three million units of r-IFN-alpha2b were administered subcutaneously every week for 12 weeks. Before and after treatment, and during a 30-month follow-up period, the patients underwent clinical and radiological examination, together with bacteriological, immunological and routine laboratory testing. RESULTS: Two of the five patients became long-term sputum smear and culture negative after r-IFN-alpha2b therapy; one of the patients showed clinical improvement and negative smear after therapy, but remained culture positive. The other two patients showed no response. CONCLUSION: The results of this trial suggest that r-IFN-alpha2b should be evaluated further in multidrug-resistant tuberculosis in prospective controlled trials.

A one-million-year-old Homo cranium from the Danakil (Afar) Depression of Eritrea.

One of the most contentious topics in the study of human evolution is that of the time, place and mode of origin of Homo sapiens. The discovery in the Northern Danakil (Afar) Depression, Eritrea, of a well-preserved Homo cranium with a mixture of characters typical of H. erectus and H. sapiens contributes significantly to this debate. The cranium was found in a succession of fluvio-deltaic and lacustrine deposits and is associated with a rich mammalian fauna of early to early-middle Pleistocene age. A magnetostratigraphic survey indicates two reversed and two normal magnetozones. The layer in which the cranium was found is near the top of the lower normal magnetozone, which is identified as the Jaramillo subchron. Consequently, the human remains can be dated at approximately 1 million years before present.

Resistencia única a Rifampicina en Tuberculosis asociada al Síndrome de Inmunodeficiencia Adquirida / Single resistance at Rifampicin in Tuberculosis associated at Acquired Immunodeficiency Syndrome

Se analizaron las historias clínicas de 12 pacientes de Tuberculosis con resistencia única a rifampicina asociada al Síndrome de Inmunodeficiencia Adquirida, cuyas muestras biológicas fueron estudiadas en el Laboratorio de Bacteriología "Dr. A. Cetrángolo" durante el período comprendido entre julio de 1991 y febrero de 1994. De los 12 pacientes, 11 eran hombres y 1 pertenecía al sexo femenino. La edad estuvo comprendida entre los 20 y 35 años. Los 10 pacientes con conducta de riesgo conocida eran adictos a drogas intravenosas. La tuberculosis fue pulmonar en 8 pacientes, extrapulmonar en 3 y localización combinada en 1 caso. (AU)

Resistencia única a Rifampicina en Tuberculosis asociada al Síndrome de Inmunodeficiencia Adquirida / Single resistance at Rifampicin in Tuberculosis associated at Acquired Immunodeficiency Syndrome

Se analizaron las historias clínicas de 12 pacientes de Tuberculosis con resistencia única a rifampicina asociada al Síndrome de Inmunodeficiencia Adquirida, cuyas muestras biológicas fueron estudiadas en el Laboratorio de Bacteriología "Dr. A. Cetrángolo" durante el período comprendido entre julio de 1991 y febrero de 1994. De los 12 pacientes, 11 eran hombres y 1 pertenecía al sexo femenino. La edad estuvo comprendida entre los 20 y 35 años. Los 10 pacientes con conducta de riesgo conocida eran adictos a drogas intravenosas. La tuberculosis fue pulmonar en 8 pacientes, extrapulmonar en 3 y localización combinada en 1 caso.

[Chronic obstructive pulmonary disease]. / Enfermedad pulmonar obstructiva crónica. Consenso argentino.

Several meetings of chest specialists were held in order to update basic knowledge on Chronic Obstructive Pulmonary Disease (COPD) and to establish guidelines regarding its prevention and treatment. This Consensus was prompted by the important morbidity and mortality due to COPD. Pulmonary emphysema, chronic bronchitis and asthma may evolve into COPD when developing chronic, persistent, non reversible airflow obstruction. Its pathologic features, physiopathology, pulmonary function derangements and clinico-radiological picture are summarized. Early detection and prevention accomplished through smoking cessation are essential to stop health damage due to this condition. Strategies directed to smoking cessation are described. Once COPD is established, inhaled bronchodilators (IB)--anticholinergics, beta-2 agonists or both--might be useful. Teophylline is indicated additionally when no improvement is obtained with IB. Inhaled steroids (IE) may stop progression of airways obstruction; they are recommended in patients who remain symttomatic and/or with severe airflow obstruction (FEV1 less than 50% predicted) despite treatment with beta-2 adrenergics and teophylline. Vaccination against influenza and pneumococcal pneumonia is suggested. Other medications (antibiotics, psychoactive drugs, alpha-1 antitrypsine, respiratory stimulants) or surgical interventions, including lung transplantation, might be of help in certain circumstances. In patients with physiotherapy, supplementary nutrition, muscle retraining, prolonged oxygen therapy and, eventually, noninvasive mechanical ventilation might improve survival and quality of life. Acute decompensations leading to respiratory failure should be promptly detected and treated with oxygen, IB, teophylline, corticosteroids, antibiotics and, eventually, mechanical ventilation. The main role of public education in disease prevention is emphasized. Moreover, patient and family education is essential for adequate treatment of COPD.

Enfermedad pulmonar obstructiva crónica. Consenso argentino. / [Chronic obstructive pulmonary disease]

Several meetings of chest specialists were held in order to update basic knowledge on Chronic Obstructive Pulmonary Disease (COPD) and to establish guidelines regarding its prevention and treatment. This Consensus was prompted by the important morbidity and mortality due to COPD. Pulmonary emphysema, chronic bronchitis and asthma may evolve into COPD when developing chronic, persistent, non reversible airflow obstruction. Its pathologic features, physiopathology, pulmonary function derangements and clinico-radiological picture are summarized. Early detection and prevention accomplished through smoking cessation are essential to stop health damage due to this condition. Strategies directed to smoking cessation are described. Once COPD is established, inhaled bronchodilators (IB)--anticholinergics, beta-2 agonists or both--might be useful. Teophylline is indicated additionally when no improvement is obtained with IB. Inhaled steroids (IE) may stop progression of airways obstruction; they are recommended in patients who remain symttomatic and/or with severe airflow obstruction (FEV1 less than 50

predicted) despite treatment with beta-2 adrenergics and teophylline. Vaccination against influenza and pneumococcal pneumonia is suggested. Other medications (antibiotics, psychoactive drugs, alpha-1 antitrypsine, respiratory stimulants) or surgical interventions, including lung transplantation, might be of help in certain circumstances. In patients with physiotherapy, supplementary nutrition, muscle retraining, prolonged oxygen therapy and, eventually, noninvasive mechanical ventilation might improve survival and quality of life. Acute decompensations leading to respiratory failure should be promptly detected and treated with oxygen, IB, teophylline, corticosteroids, antibiotics and, eventually, mechanical ventilation. The main role of public education in disease prevention is emphasized. Moreover, patient and family education is essential for adequate treatment of COPD.

Enfermedad pulmonar obstructiva cronica / Chronic obstructive pulmonary disease

Dada la importante morbilidad y mortalidad de la Enfermedad Pulmonar Obstructiva Crónica (EPOC) se llevaron a cabo reiterados encuentros de especialistas em medicina respiratoria a fin de actualizar en un Consenso conocimientos básicos acerca de esta afección y efectuar recomendaciones para su prevención y tratameinto. Se incluyen dentro de la EPOC fases evolutivas del enfisema pulmonar, bronquitis crónica y asma bronquial resumiéndose sus alteraciones patológicas, fisiopatogenia, presentación clínico-radiológica y evaluación funcional. Su detección precoz y prevención a través de la cesación del hábito de fumar son esenciales para detener los daños causados por esta afección. Se describen las estrategias que componen un programa de interrupción del hábito. Una vez establecida la EPOC la administración de broncodilatadores inhalatorios (BI) - anticolinérgicos, estimulantes beta-2 adrenérgicos, o ambos - puede ser útil. La teofilina es indicada adicionalmente cuando no existe satisfactoria mejoría con aquellos. La administración de corticoides por vía inhalatoria podría atenuar la evolución de la obstrucción y se recomienda en los pacientes sintomáticos y/o con obstrucción severa al flujo aéreo, a pesar del tratamiento con BI y teofilina. La vacunación antigripal y antineumocóccica es sugerida si bien no hay pruebas concluyentes acerca de su eficacia. Otras medicaciones (antibióticos, drogas psicoactivas, alfa 1 antitripsina, estimulantes respiratorios) o intervenciones quirúrgicas hasta el transplante de pulmón se recomiendan en determinadas circunstancias (AU)

Enfermedad pulmonar obstructiva cronica / Chronic obstructive pulmonary disease

Dada la importante morbilidad y mortalidad de la Enfermedad Pulmonar Obstructiva Crónica (EPOC) se llevaron a cabo reiterados encuentros de especialistas em medicina respiratoria a fin de actualizar en un Consenso conocimientos básicos acerca de esta afección y efectuar recomendaciones para su prevención y tratameinto. Se incluyen dentro de la EPOC fases evolutivas del enfisema pulmonar, bronquitis crónica y asma bronquial resumiéndose sus alteraciones patológicas, fisiopatogenia, presentación clínico-radiológica y evaluación funcional. Su detección precoz y prevención a través de la cesación del hábito de fumar son esenciales para detener los daños causados por esta afección. Se describen las estrategias que componen un programa de interrupción del hábito. Una vez establecida la EPOC la administración de broncodilatadores inhalatorios (BI) - anticolinérgicos, estimulantes beta-2 adrenérgicos, o ambos - puede ser útil. La teofilina es indicada adicionalmente cuando no existe satisfactoria mejoría con aquellos. La administración de corticoides por vía inhalatoria podría atenuar la evolución de la obstrucción y se recomienda en los pacientes sintomáticos y/o con obstrucción severa al flujo aéreo, a pesar del tratamiento con BI y teofilina. La vacunación antigripal y antineumocóccica es sugerida si bien no hay pruebas concluyentes acerca de su eficacia. Otras medicaciones (antibióticos, drogas psicoactivas, alfa 1 antitripsina, estimulantes respiratorios) o intervenciones quirúrgicas hasta el transplante de pulmón se recomiendan en determinadas circunstancias

Normas establecidas por consenso para el tratamiento del asma bronquial y sus exacerbaciones / Standards established by consensus for the treatment of bronchial asthma and its exacerbations

A group of pulmonologists from different sites of Argentina convened to establish consensus guidelines for treatment of acute and chronic bronchial asthma. General acceptance that in fatal asthma diagnosis and hospital admission are usually too late and treatment insufficient prompted the need for this meeting. The purpose of treatment was devised to keep the patient symptomless, decrease frequency of exacerbations and the risk of severe attacks. Peak expiratory flow rate (PEFR) measurement in all patients was decided. inhalation of anti-inflammatory drugs (corticosteroids, CE, and/or disodium cromoglycate, DSG, in those younger than 20 years) was established as first line of treatment. Inhaled CE (even in high doses such as 2 mg/day) do not provoke significant adverse systemic effects (immune depression, Cushing syndrome, hyperglycemia in diabetics or osteopenia). Secondary local adverse effects are however frequent: oral and pharyngeal candidiasis and dysphonia. It is advisable considering present evidence, that bronchodilators (Bd) be used preferentially on demand. On account of small bronchodilator effect and frequent secondary adverse effects, use of theophylline should be limited to patients not adequately responsive to anti-inflammatory drugs in high dosage. Immunotherapy is not useful in asthma. Four clinical levels were defined in chronic asthma considering severity of dyspnea, frequency of nocturnal bronchial obstruction, levels of PEFR and amount of required Bd. Guidelines of treatment were established for each clinical level considering increasing dosage of CGS, inhaled CE (up to 2 mg/day) and regular administration of Bd. Indications for systemic CE administration were also established. Three levels of acute asthma (sudden worsening of symptoms) were accepted based on clinical evidence and PEFR values. Treatment was quantitatively adjusted to severity. Criteria for hospital admission either in emergency or intensive care areas and treatment procedures were established.(Au)

Normas establecidas por consenso para el tratamiento del asma bronquial y sus exacerbaciones / Standards established by consensus for the treatment of bronchial asthma and its exacerbations

A group of pulmonologists from different sites of Argentina convened to establish consensus guidelines for treatment of acute and chronic bronchial asthma. General acceptance that in fatal asthma diagnosis and hospital admission are usually too late and treatment insufficient prompted the need for this meeting. The purpose of treatment was devised to keep the patient symptomless, decrease frequency of exacerbations and the risk of severe attacks. Peak expiratory flow rate (PEFR) measurement in all patients was decided. inhalation of anti-inflammatory drugs (corticosteroids, CE, and/or disodium cromoglycate, DSG, in those younger than 20 years) was established as first line of treatment. Inhaled CE (even in high doses such as 2 mg/day) do not provoke significant adverse systemic effects (immune depression, Cushing syndrome, hyperglycemia in diabetics or osteopenia). Secondary local adverse effects are however frequent: oral and pharyngeal candidiasis and dysphonia. It is advisable considering present evidence, that bronchodilators (Bd) be used preferentially on demand. On account of small bronchodilator effect and frequent secondary adverse effects, use of theophylline should be limited to patients not adequately responsive to anti-inflammatory drugs in high dosage. Immunotherapy is not useful in asthma. Four clinical levels were defined in chronic asthma considering severity of dyspnea, frequency of nocturnal bronchial obstruction, levels of PEFR and amount of required Bd. Guidelines of treatment were established for each clinical level considering increasing dosage of CGS, inhaled CE (up to 2 mg/day) and regular administration of Bd. Indications for systemic CE administration were also established. Three levels of acute asthma (sudden worsening of symptoms) were accepted based on clinical evidence and PEFR values. Treatment was quantitatively adjusted to severity. Criteria for hospital admission either in emergency or intensive care areas and treatment procedures were established.

[Standards established by consensus for the treatment of bronchial asthma and its exacerbations]. / Normas establecidas por consenso para el tratamiento del asma bronquial y sus exacerbaciones.

A group of pulmonologists from different sites of Argentina convened to establish consensus guidelines for treatment of acute and chronic bronchial asthma. General acceptance that in fatal asthma diagnosis and hospital admission are usually too late and treatment insufficient prompted the need for this meeting. The purpose of treatment was devised to keep the patient symptomless, decrease frequency of exacerbations and the risk of severe attacks. Peak expiratory flow rate (PEFR) measurement in all patients was decided. inhalation of anti-inflammatory drugs (corticosteroids, CE, and/or disodium cromoglycate, DSG, in those younger than 20 years) was established as first line of treatment. Inhaled CE (even in high doses such as 2 mg/day) do not provoke significant adverse systemic effects (immune depression, Cushing syndrome, hyperglycemia in diabetics or osteopenia). Secondary local adverse effects are however frequent: oral and pharyngeal candidiasis and dysphonia. It is advisable considering present evidence, that bronchodilators (Bd) be used preferentially on demand. On account of small bronchodilator effect and frequent secondary adverse effects, use of theophylline should be limited to patients not adequately responsive to anti-inflammatory drugs in high dosage. Immunotherapy is not useful in asthma. Four clinical levels were defined in chronic asthma considering severity of dyspnea, frequency of nocturnal bronchial obstruction, levels of PEFR and amount of required Bd. Guidelines of treatment were established for each clinical level considering increasing dosage of CGS, inhaled CE (up to 2 mg/day) and regular administration of Bd. Indications for systemic CE administration were also established. Three levels of acute asthma (sudden worsening of symptoms) were accepted based on clinical evidence and PEFR values. Treatment was quantitatively adjusted to severity. Criteria for hospital admission either in emergency or intensive care areas and treatment procedures were established.

Normas establecidas por consenso para el tratamiento del asma bronquial y sus exacerbaciones. / [Standards established by consensus for the treatment of bronchial asthma and its exacerbations]

A group of pulmonologists from different sites of Argentina convened to establish consensus guidelines for treatment of acute and chronic bronchial asthma. General acceptance that in fatal asthma diagnosis and hospital admission are usually too late and treatment insufficient prompted the need for this meeting. The purpose of treatment was devised to keep the patient symptomless, decrease frequency of exacerbations and the risk of severe attacks. Peak expiratory flow rate (PEFR) measurement in all patients was decided. inhalation of anti-inflammatory drugs (corticosteroids, CE, and/or disodium cromoglycate, DSG, in those younger than 20 years) was established as first line of treatment. Inhaled CE (even in high doses such as 2 mg/day) do not provoke significant adverse systemic effects (immune depression, Cushing syndrome, hyperglycemia in diabetics or osteopenia). Secondary local adverse effects are however frequent: oral and pharyngeal candidiasis and dysphonia. It is advisable considering present evidence, that bronchodilators (Bd) be used preferentially on demand. On account of small bronchodilator effect and frequent secondary adverse effects, use of theophylline should be limited to patients not adequately responsive to anti-inflammatory drugs in high dosage. Immunotherapy is not useful in asthma. Four clinical levels were defined in chronic asthma considering severity of dyspnea, frequency of nocturnal bronchial obstruction, levels of PEFR and amount of required Bd. Guidelines of treatment were established for each clinical level considering increasing dosage of CGS, inhaled CE (up to 2 mg/day) and regular administration of Bd. Indications for systemic CE administration were also established. Three levels of acute asthma (sudden worsening of symptoms) were accepted based on clinical evidence and PEFR values. Treatment was quantitatively adjusted to severity. Criteria for hospital admission either in emergency or intensive care areas and treatment procedures were established.