Login to your account

Username *
Password *
Remember Me

Blog With Right Sidebar

Faster for less: the new "shorter" regimen for multidrug-resistant tuberculosis

Multidrug resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) are growing clinical and public health concerns, with an estimated worldwide incidence and mortality of 480 000 and 190 000 cases, respectively (2014) [1]. The World Health Organization (WHO) End TB Strategy reiterates the MDR-/XDR-TB threat and the solutions to control the epidemic [2]. Unfortunately, large proportions of patients with resistant TB do not have access to adequate diagnostics and treatment yet, while treatment success rates remain suboptimal (as demonstrated in the largest retrospective cohort of MDR-TB patients, i.e., TB caused by Mycobacterium tuberculosis isolates resistant to at least isoniazid and rifampicin) and decrease further with resistance patterns beyond XDR-TB [3].

Surgical lung biopsy for the diagnosis of interstitial lung disease in England: 1997-2008

International guidelines and new targeted therapies for idiopathic pulmonary fibrosis have increased the need for accurate diagnosis of interstitial lung disease (ILD), which may lead to more surgical lung biopsies. This study aimed to assess the risk of this procedure in patients from the UK.

We used Hospital Episodes Statistics data from 1997 to 2008 to assess the frequency of surgical lung biopsy for ILD in England, UK. We identified cardiothoracic surgical patients using International Classification of Diseases revision 10 codes for ILD and Office of Population Censuses and Surveys Classification of Interventions and Procedures version 4 codes for surgical lung biopsy. We excluded those with lung resections or lung cancer. We estimated in-hospital, 30-day and 90-day mortality following the procedure, and linked to cause of death using data from the UK Office of National Statistics.

We identified 2820 patients with ILD undergoing surgical lung biopsy during the 12-year period. The number of biopsies increased over the time period studied. In-hospital, 30-day and 90-day mortality were 1.7%, 2.4% and 3.9%, respectively. Male sex, increasing age, increasing comorbidity and open surgery were risk factors for mortality.

Surgical lung biopsy for ILD has a similar mortality to lobectomy for lung cancer, and clinicians and patients should understand the likely risks involved.

Mast cells are associated with exacerbations and eosinophilia in children with severe asthma

The role of mast cells in the pathogenesis of childhood asthma is poorly understood. We aimed to estimate the implication of airway mucosal mast cells in severe asthma and their relationship with clinical, functional, inflammatory and remodelling parameters.

Bronchial biopsies were performed in 36 children (5–18 years) with severe asthma: 24 had frequent severe exacerbations and/or daily symptoms in the previous year (symptomatic group), and 12 had few symptoms and a persistent obstructive pattern (paucisymptomatic group). Nine children without asthma were included as control subjects. We assessed mast cells in the submucosa and airway smooth muscle using c-kit antibodies and in the entire biopsy area using Giemsa.

The number of submucosal mast cells was higher in the symptomatic group than in the paucisymptomatic group (p=0.02). The number of submucosal mast cells correlated with the number of severe exacerbations (p=0.02, r=0.37). There were positive correlations between the number of submucosal mast cells (p<0.01, r=0.44), airway smooth muscle mast cells (p=0.02, r= 0.40), mast cells stained by Giemsa (p<0.01, r=0.44) and submucosal eosinophils.

Mast cells are associated with severe exacerbations and submucosal eosinophilic inflammation in children with severe asthma.

First evaluation of QuantiFERON-TB Gold Plus performance in contact screening

Identifying latently infected individuals is crucial for the elimination of tuberculosis (TB). We evaluated for the first time the performance of a new type of interferon- release assay, QuantiFERON-TB Plus (QFT-Plus), which includes an additional antigen tube (TB2), stimulating both CD4+ and CD8+ T-cells in contacts of TB patients.

Contacts were screened for latent TB infection by tuberculin skin test, QFT-Plus and QuantiFERON-TB Gold in Tube (QFT-GIT).

In 119 TB contacts, the overall agreement between QFT-Plus and QFT-GIT was high, with a Cohen's of 0.8. Discordant results were found in 12 subjects with negative QFT-GIT and positive QFT-Plus results. In analyses of markers of TB exposure and test results, the average time spent with the index case was the strongest risk factor for positivity in each of these tests. The difference in interferon- production between the two antigen tubes (TB2–TB1) was used as an estimate of CD8+ stimulation provided by the TB2. TB2–TB1 values >0.6 IU·mL–1 were significantly associated with proximity to the index case and European origin.

QFT-Plus has a stronger association with surrogate measures of TB exposure than QFT-GIT in adults screened for latent TB infection. Interferon- response in the new antigen tube used an indirect estimate of specific CD8+ response correlates with increased Mycobacterium tuberculosis exposure, suggesting a possible role in identifying individuals with recent infection.

Severe asthma exists despite suppressed tissue inflammation: findings of the U-BIOPRED study

The U-BIOPRED study is a multicentre European study aimed at a better understanding of severe asthma. It included three steroid-treated adult asthma groups (severe nonsmokers (SAn group), severe current/ex-smokers (SAs/ex group) and those with mild–moderate disease (MMA group)) and healthy controls (HC group). The aim of this cross-sectional, bronchoscopy substudy was to compare bronchial immunopathology between these groups.

In 158 participants, bronchial biopsies and bronchial epithelial brushings were collected for immunopathologic and transcriptomic analysis. Immunohistochemical analysis of glycol methacrylate resin-embedded biopsies showed there were more mast cells in submucosa of the HC group (33.6 mm–2) compared with both severe asthma groups (SAn: 17.4 mm–2, p<0.001; SAs/ex: 22.2 mm–2, p=0.01) and with the MMA group (21.2 mm–2, p=0.01). The number of CD4+ lymphocytes was decreased in the SAs/ex group (4.7 mm–2) compared with the SAn (11.6 mm–2, p=0.002), MMA (10.1 mm–2, p=0.008) and HC (10.6 mm–2, p<0.001) groups. No other differences were observed.

Affymetrix microarray analysis identified seven probe sets in the bronchial brushing samples that had a positive relationship with submucosal eosinophils. These mapped to COX-2 (cyclo-oxygenase-2), ADAM-7 (disintegrin and metalloproteinase domain-containing protein 7), SLCO1A2 (solute carrier organic anion transporter family member 1A2), TMEFF2 (transmembrane protein with epidermal growth factor like and two follistatin like domains 2) and TRPM-1 (transient receptor potential cation channel subfamily M member 1); the remaining two are unnamed.

We conclude that in nonsmoking and smoking patients on currently recommended therapy, severe asthma exists despite suppressed tissue inflammation within the proximal airway wall.

Search