Doenças intersticiais pulmonares no CTI: Quando pensar? Como conduzir? / Interstitial lung disease in ICU: When to think? How to manage?

As doenças intersticiais pulmonares podem ser secundárias a um processo agudo ou resultar de uma inflamação e cicatrização progressiva do parênquima pulmonar. Elas podem ser desafiadoras na terapia intensiva, tanto para o diagnóstico quanto para o tratamento. A exclusão de causas reversíveis de insuficiência respiratória e medidas de suporte são os pontos principais da terapia. É fundamental a revisão das imagens radiológicas prévias e a realização de anamnese detalhada. A coleta de lavado broncoalveolar por broncoscopia e/ou biopsia cirúrgica podem ser necessárias. Nas exacerbações agudas é recomendado corticosteróide e antibióticos. Frequentemente é necessária a ventilação mecânica para melhorar a troca gasosa e a baixa complacência pulmonar. A insuficiência respiratória é um final comum das doenças intersticiais crônicas e apresentam um mau prognóstico. Devido a isto, a ventilação mecânica deve ser oferecida nos casos com processos patológicos reversíveis ou nos candidatos à transplante pulmonar...

Interstitial lung disease (ILD) can be an acute process or the result of progressive inflammation and scarring of the pulmonary parenchyma. They can be challenging in the ICU both to diagnose and treatment. Exclusion of reversible causes of respiratory failure while administering supportive care are the mainstay treatment of patients with ILD with respiratory failure. It is fundamental to review previous imaging, detailed medication and occupational history. Bronchoscopy with bronchoalveolar lavage and/or surgical lung biopsy may be recommended. If an exacerbation syndrome is identified, corticosteroids and antibiotics are advised. Often mechanical ventilation is needed to control poor compliance and gas exchange. Respiratory failure is a common end of chronic ILD and carries a poor outcome. Mechanical ventilation should only be offered in select cases, most notably patients with reversible processes or those considered candidates for lung transplantation...

Status Asmaticus: lenda ou realidade? Como tratar melhor? / Status Asmathicus: legend or reality? How to treat better?

A história natural do status asmaticus é na maioria das vezes de resolução com mortalidade geral menor que 1%. Cerca de 80% dos pacientes com exacerbação de asma brônquica são liberados da emergência nas primeiras duas horas de tratamento. No entanto, nos pacientes com necessidade de ventilação mecânica a mortalidade pode chegar a 8%. O tratamento rápido e eficaz é essencial para o sucesso do tratamento e a prevenção de complicações. Neste artigo são abordadas as recomendações atuais do tratamento das exacerbações graves de asma brônquica nos setores de emergência e terapia intensiva...

The natural history of status asthmaticus is, most of the time, sorted out with overall mortality less than 1%. About 80% of patients with exacerbation of asthma emergency are released within the first two hours of treatment. However, in patients requiring mechanical ventilation mortality can reach 8%. The rapid and effective treatment is essential for the success of the treatment and the prevention of complications. This paper addresses the current recommendations the treatment of severe exacerbations of asthma in the emergency department and intensive care...

Mycobacterium tuberculosis of the RDRio genotype is the predominant cause of tuberculosis and associated with multidrug resistance in Porto Alegre City, South Brazil.

Spoligotyping has shown Mycobacterium tuberculosis strains to be composed of different lineages, and some of them are not just geographically restricted but also affect specific ethnic populations and are associated with outbreaks and drug resistance. We recently described a particular subtype within the Latin American-Mediterranean (LAM) family, called RD(Rio), widespread in Brazil. Moreover, recent data also indicate that RD(Rio) is present in many countries on all continents and is associated with cavitary disease and multidrug resistance (MDR). To further explore the relationship between RD(Rio) and MDR, we conducted a study in a tuberculosis (TB) reference center responsible for the care of MDR patients in Rio Grande do Sul, the southernmost Brazilian state. From a collection of 237 clinical isolates, RD(Rio) alone was responsible for one-half of all MDR cases, including one large group composed of strains with identical IS6110-restriction fragment length polymorphism (RFLP) and having the LAM5 signature. We additionally had complete data records for 96 patients and could make comparisons between the presence and absence of RD(Rio). No difference in clinical, radiological or laboratory features was observed, but a significantly greater number of cases with MDR were described in patients infected with an RD(Rio) strain (P = 0.0015). Altogether, RD(Rio) was responsible for 38% of all TB cases. These data support and confirmed previous findings that RD(Rio) is the main agent responsible for TB in Brazil and is associated with drug resistance. Considering that RD(Rio) is a globally distributed genotype, such findings raise concern about the increase in MDR in certain human populations.

The total face mask is more comfortable than the oronasal mask in noninvasive ventilation but is not associated with improved outcome.

BACKGROUND: Noninvasive positive-pressure ventilation (NPPV) is commonly used to improve ventilation and oxygenation and avoid endotracheal intubation and mechanical ventilation. Although clinically indicated, most patients fail to use NPPV due to mask intolerance. A total face mask was designed to increase compliance, but whether this translates into better outcome (improvement in clinical and blood gas parameters and less intubation) is unknown. OBJECTIVES: We compared the evolution of the clinical parameters, blood gases, levels of ventilatory support and rate of endotracheal intubation using the total face mask or the traditional oronasal mask during NPPV. METHODS: A total of 60 patients were randomized to use either mask during NPPV. The clinical and laboratory parameters, as well as the level of ventilatory support were recorded at different intervals in both groups for up to 6 h. In addition, the tolerance for each mask and the need for endotracheal intubation were compared. RESULTS: Patients tolerated the total face mask significantly better (p = 0.0010) and used NPPV for a longer time (p = 0.0017) when compared with the oronasal mask. Just 1 patient switched to the total face mask because of intolerance. Although better tolerated, the rate of endotracheal intubation was similar in both groups (p = 0.4376), as was the clinical and laboratory evolution. CONCLUSIONS: The total face mask was more comfortable, allowing the patients to tolerate NPPV longer; however, these accomplishments did not translate into a better outcome. Due to its comfort, the total face mask should be available, at least as an option, in units where NPPVs are routinely applied.

RDRio Mycobacterium tuberculosis infection is associated with a higher frequency of cavitary pulmonary disease.

Molecular genotyping has shown Mycobacterium tuberculosis lineages to be geographically restricted and associated with distinct ethnic populations. Whether tuberculosis (TB) caused by some M. tuberculosis lineages can present with a differential clinical spectrum is controversial because of very limited clinical data. We recently reported on the discovery of RD(Rio) M. tuberculosis, a Latin American-Mediterranean sublineage that is the predominant cause of TB in Rio de Janeiro, Brazil. To investigate the clinical attributes of TB caused by RD(Rio) strains, we studied a cohort of TB cases from Belo Horizonte, Brazil, in which clinical information recorded on a standardized questionnaire was collected at the time of microbiological testing. These patients were referred for culture and drug susceptibility testing because of the clinical suspicion of "complicated" TB, as demonstrated by high rates of multidrug resistance (12%) and cavitary TB (80%). We performed spoligotyping and RD(Rio) genotyping on the M. tuberculosis strains and analyzed the clinical data from these patients. RD(Rio) M. tuberculosis accounted for 37% of the total TB burden. Multivariate analysis found a significant association between TB caused by RD(Rio) strains and pulmonary cavitation and residence in Belo Horizonte. Since cavitary TB is associated with higher sputum bacillary load, our findings support the hypothesis that RD(Rio) M. tuberculosis is associated with a more "severe" disease as a strategy to increase transmission. Future studies are needed to confirm these observations and to better define the contribution of RD(Rio) M. tuberculosis to the global TB epidemic.

Application of sensitive and specific molecular methods to uncover global dissemination of the major RDRio Sublineage of the Latin American-Mediterranean Mycobacterium tuberculosis spoligotype family.

The Latin American-Mediterranean (LAM) family of Mycobacterium tuberculosis is believed to be the cause of approximately 15% of tuberculosis cases worldwide. Previously, we defined a prevalent sublineage of the LAM family in Brazil by a single characteristic genomic deletion designated RD(Rio). Using the Brazilian strains, we pinpoint an Ag85C(103) single nucleotide polymorphism (SNP) (screened by restriction fragment length polymorphism [RFLP] analysis) that correctly identified all LAM family strains. Importantly, all RD(Rio) strains concomitantly possessed the RD174 deletion. These genetic signatures, along with a newly developed multiplex PCR for rapid differentiation between "wild-type" and RD(Rio) strains, were then used to analyze an international collection of M. tuberculosis strains. RD(Rio) M. tuberculosis was identified from four continents involving 11 countries. Phylogenetic analysis of the IS6110-RFLP patterns from representative RD(Rio) and LAM strains from Brazil, along with all representative clusters from a South African database, confirmed their genetic relatedness and transcontinental transmission. The Ag85C(103) SNP RFLP, as compared to results obtained using a PCR method targeting a LAM-restricted IS6110 element, correctly identified 99.8% of LAM spoligotype strains. Together, these tests were more accurate than spoligotyping at categorizing strains with indefinable spoligotypes and segregated true LAM strains from those with convergent spoligotypes. The fact that RD(Rio) strains were identified worldwide highlights the importance of this LAM family sublineage and suggests that this strain is a global threat that should be specifically targeted by public health resources. Our provision of simple and robust molecular methods will assist the evaluation of the LAM family and the RD(Rio) sublineage.

Necrotizing sarcoid granulomatosis in a family of patients with sarcoidosis reinforces the association between both entities.

Necrotizing sarcoid granulomatosis (NSG) is a rare entity mainly characterized by a prominent granulomatous vasculitis affecting middle-aged or old individuals and with a favorable prognosis. Although many believe it is a variant of sarcoidosis, the proper classification is still a matter of debate as some of its features are found in sarcoidosis but also in Churg-Strauss syndrome, Wegener's disease and hypersensitivity pneumonitis. In this paper, we described for the first time a case of NSG in a family with several cases of sarcoidosis, reinforcing the relationship between NSG and sarcoidosis. Additional interesting findings were the young age of the patient (15 years old), the symptoms limited to the respiratory tract (uncommon when NSG affects youngsters) and the increase in serologic markers of autoimmune disease. Though complete criteria for autoimmune disease were not present, systemic lupus erythematosus and Sjogren's syndrome are possible candidates. As sarcoidosis is described to be associated with several autoimmune diseases, this finding is an additional suggestion of the relationship between both entities.

Discovery of a novel Mycobacterium tuberculosis lineage that is a major cause of tuberculosis in Rio de Janeiro, Brazil.

The current study evaluated Mycobacterium tuberculosis isolates from Rio de Janeiro, Brazil, for genomic deletions. One locus in our panel of PCR targets failed to amplify in approximately 30% of strains. A single novel long sequence polymorphism (>26.3 kb) was characterized and designated RD(Rio). Homologous recombination between two similar protein-coding genes is proposed as the mechanism for deleting or modifying 10 genes, including two potentially immunogenic PPE proteins. The flanking regions of the RD(Rio) locus were identical in all strains bearing the deletion. Genetic testing by principal genetic group, spoligotyping, variable-number tandem repeats of mycobacterial interspersed repetitive units (MIRU-VNTR), and IS6110-based restriction fragment length polymorphism analysis cumulatively support the idea that RD(Rio) strains are derived from a common ancestor belonging solely to the Latin American-Mediterranean spoligotype family. The RD(Rio) lineage is therefore the predominant clade causing tuberculosis (TB) in Rio de Janeiro and, as indicated by genotypic clustering in MIRU-VNTR analysis, the most significant source of recent transmission. Limited retrospective reviews of bacteriological and patient records showed a lack of association with multidrug resistance or specific risk factors for TB. However, trends in the data did suggest that RD(Rio) strains may cause a form of TB with a distinct clinical presentation. Overall, the high prevalence of this genotype may be related to enhanced virulence, transmissibility, and/or specific adaptation to a Euro-Latin American host population. The identification of RD(Rio) strains outside of Brazil points to the ongoing intercontinental dissemination of this important genotype. Further studies are needed to determine the differential strain-specific features, pathobiology, and worldwide prevalence of RD(Rio) M. tuberculosis.

Novel genetic polymorphisms that further delineate the phylogeny of the Mycobacterium tuberculosis complex.

In a previous report, we described a PCR protocol for the differentiation of the various species of the Mycobacterium tuberculosis complex (MTC) on the basis of genomic deletions (R. C. Huard, L. C. de Oliveira Lazzarini, W. R. Butler, D. van Soolingen, and J. L. Ho, J. Clin. Microbiol. 41:1637-1650, 2003). That report also provided a broad cross-comparison of several previously identified, phylogenetically relevant, long-sequence and single-nucleotide polymorphisms (LSPs and SNPs, respectively). In the present companion report, we expand upon the previous work (i) by continuing the evaluation of known MTC phylogenetic markers in a larger collection of tubercle bacilli (n = 125), (ii) by evaluating additional recently reported MTC species-specific and interspecific polymorphisms, and (iii) by describing the identification and distribution of a number of novel LSPs and SNPs. Notably, new genomic deletions were found in various Mycobacterium tuberculosis strains, new species-specific SNPs were identified for "Mycobacterium canettii," Mycobacterium microti, and Mycobacterium pinnipedii, and, for the first time, intraspecific single-nucleotide DNA differences were discovered for the dassie bacillus, the oryx bacillus, and the two Mycobacterium africanum subtype I variants. Surprisingly, coincident polymorphisms linked one M. africanum subtype I genotype with the dassie bacillus and M. microti with M. pinnipedii, thereby suggesting closer evolutionary ties within each pair of species than had been previously thought. Overall, the presented data add to the genetic definitions of several MTC organisms as well as fine-tune current models for the evolutionary history of the MTC.

Down-modulation of lung immune responses by interleukin-10 and transforming growth factor beta (TGF-beta) and analysis of TGF-beta receptors I and II in active tuberculosis.

Immune factors influencing progression to active tuberculosis (TB) remain poorly defined. In this study, we investigated the expression of immunoregulatory cytokines and receptors by using lung bronchoalveolar lavage cells obtained from patients with pulmonary TB, patients with other lung diseases (OLD patients), and healthy volunteers (VOL) by using reverse transcriptase PCR, a transforming growth factor beta (TGF-beta) bioactivity assay, and an enzyme immunoassay. TB patients were significantly more likely than OLD patients to coexpress TGF-beta receptor I (RI) and RII mRNA, as well as interleukin-10 (IL-10) mRNA (thereby indicating the state of active gene transcription in the alveolar cells at harvest). In contrast, gamma interferon (IFN-gamma) and IL-2 mRNA was seen in both TB and OLD patients. Likewise, significantly elevated pulmonary steady-state protein levels of IL-10, IFN-gamma, and bioactive TGF-beta were found in TB patients versus those in OLD patients and VOL. These data suggest that the combined production of the immunosuppressants IL-10 and TGF-beta, as well as coexpression of TGF-beta RI and RII (required for cellular response to TGF-beta), may act to down-modulate host anti-Mycobacterium tuberculosis immunity and thereby allow uncontrolled bacterial replication and overt disease. Delineating the underlying mechanisms of M. tuberculosis-triggered expression of these immune elements may provide a molecular-level understanding of TB immunopathogenesis.

The Mycobacterium tuberculosis complex-restricted gene cfp32 encodes an expressed protein that is detectable in tuberculosis patients and is positively correlated with pulmonary interleukin-10.

Human tuberculosis (TB) is caused by the bacillus Mycobacterium tuberculosis, a subspecies of the M. tuberculosis complex (MTC) of mycobacteria. Postgenomic dissection of the M. tuberculosis proteome is ongoing and critical to furthering our understanding of factors mediating M. tuberculosis pathobiology. Towards this end, a 32-kDa putative glyoxalase in the culture filtrate (CF) of growing M. tuberculosis (originally annotated as Rv0577 and hereafter designated CFP32) was identified, cloned, and characterized. The cfp32 gene is MTC restricted, and the gene product is expressed ex vivo as determined by the respective Southern and Western blot testing of an assortment of mycobacteria. Moreover, the cfp32 gene sequence is conserved within the MTC, as no polymorphisms were found in the tested cfp32 PCR products upon sequence analysis. Western blotting of M. tuberculosis subcellular fractions localized CFP32 predominantly to the CF and cytosolic compartments. Data to support the in vivo expression of CFP32 were provided by the serum recognition of recombinant CFP32 in 32% of TB patients by enzyme-linked immunosorbent assay (ELISA) as well as the direct detection of CFP32 by ELISA in the induced sputum samples from 56% of pulmonary TB patients. Of greatest interest was the observation that, per sample, sputum CFP32 levels (a potential indicator of increasing bacterial burden) correlated with levels of expression in sputum of interleukin-10 (an immunosuppressive cytokine and a putative contributing factor to disease progression) but not levels of gamma interferon (a key cytokine in the protective immune response in TB), as measured by ELISA. Combined, these data suggest that CFP32 serves a necessary biological function(s) in tubercle bacilli and may contribute to the M. tuberculosis pathogenic mechanism. Overall, CFP32 is an attractive target for drug and vaccine design as well as new diagnostic strategies.