Respirology

Tuberculosis (TB) is an international public health priority and kills almost two million people annually. TB is out of control in Africa due to increasing poverty and HIV coinfection, and drug‐resistant TB threatens to destabilize TB control efforts in several regions of the world. Existing diagnostic tools and therapeutic interventions for TB are suboptimal. Thus, new vaccines, immunotherapeutic interventions and diagnostic tools are urgently required to facilitate TB control efforts. An improved understanding of the immunopathogenesis of TB can facilitate the identification of correlates of immune protection, the design of effective vaccines, the rational selection of immunotherapeutic agents, the evaluation of new drug candidates, and drive the development of new immunodiagnostic tools. Here we review the immunology of TB with a focus on aspects that are clinically and therapeutically relevant. An immunologically orientated approach to tackling TB can only succeed with concurrent efforts to alleviate poverty and reduce the global burden of HIV.

Abstract:  Invasive pulmonary aspergillosis (IPA) usually occurs in immunocompromised patients. However, rarely, this infection can occur in normal hosts. This review of the literature identified 13 cases of IPA associated with influenza, of which 12 had influenza A and the type of influenza was not mentioned in the other case. Reported here is a case of IPA, which was associated with influenza B, in a 63‐year‐old immunocompetent woman. Her lungs showed gross invasion and she was treated with itraconazole and amphotericin B. She required mechanical ventilation for about 5 months but recovered completely. This is the first reported case of IPA associated with influenza B.

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Transient whole‐body hyperthermia was reported to reduce lung damage in a rat with intra‐abdominal sepsis produced by caecal perforation.

Methodology: In order to determine the effect of heat shock response on acute lung injury induced by endotoxin, which plays a central role in the pathogenesis of sepsis, we instilled either saline or lipopolysaccharide (LPS) intravenously with and without heat pretreatment in rats. The heated rats had their rectal temperature raised to more than 40°C for 13 min 18 h before intravenous administration of saline or LPS.

Results: We found that the lung leak was significantly increased among the rats given LPS intravenously with (median, 0.17; range, 0.15–0.22; n = 10) and without heat pretreatment (0.23; 0.17–0.30; n = 10) compared with those of saline‐treated rats (0.13; 0.10–0.14; n = 10) (P < 0.05 in each). However, rats given LPS after heat pretreatment had significantly decreased lung leak index compared with those of LPS‐treated rats without heat pretreatment (P < 0.05). Rats administered LPS intravenously showed increased myeloperoxidase activity without heat pretreatment (19.01; 9.34–28.00 U/g; n = 10) compared with that of saline‐treated rats (7.09; 4.49–10.56 U/g; n = 5) (P < 0.05) ( Fig. 2). Myeloperoxidase activity of the rats treated with LPS with heat pretreatment (5.57; 2.87–8.96 U/g; n = 10) was significantly decreased to the level of normal control compared with that of LPS‐treated rats without heat pretreatment (P < 0.05). The levels of heat shock proteins (HSP72) in lung tissue, which were examined by western blot analysis, were increased over baseline levels at 23 h after hyperthermic stress.

Heat pretreatment decreased lung myeloperoxidase (MPO) activity in rats administered lipopolysaccharide (LPS; 3 mg/kg) intravenously. The number of determinations is shown in parentheses. *P < 0.001 compared with saline‐treated rats. **P > 0.05 compared with saline‐treated rats. Boxplot: Box = 25–75 percentile; bold line, median value; whiskers indicate the minimum and maximum values.

Objective:  Exhaled nitric oxide (eNO) has been used as a surrogate of airway inflammation in mild asthma. However, whether eNO levels reflect disease activity in symptomatic asthmatics receiving moderate doses of inhaled corticosteroid (ICS) is more uncertain.

Methodology:  To examine the relationship between eNO levels, sputum and blood eosinophils (SpE and PbE), PD₂₀ methacholine as a marker of airway hyperresponsiveness (AHR) and clinical status in 28 ICS‐treated asthmatic subjects with persistent asthma compared to that in 25 symptomatic asthmatics managed with β₂‐agonists alone.

Results:  As expected, eNO levels were normalized in ICS‐treated subjects and significantly elevated in the β₂‐agonist only group (P < 0.001). SpE, PbE and PD_20M did not differ between asthmatic groups but FEV₁ was significantly worse in ICS‐treated subjects (P < 0.01). Exhaled NO levels correlated with PbE within both asthmatic groups (P < 0.005), but with SpE only in ICS‐untreated subjects (r_(s) = 0.6, P < 0.05). In contrast, PD_20M was negatively correlated with eNO and PbE in ICS‐treated subjects only (r_(s) = − 0.4, r_(s) = − 0.4, respectively, P < 0.05). SpE and PbE were strongly correlated in both asthmatic groups (r_(s) = 0.8, r_(s) = 0.7, respectively, P < 0.005). Exhaled NO levels, SpE and PbE were all positively associated with increased nocturnal awakenings ( P < 0.05) in ICS‐treated subjects, but not in ICS‐untreated subjects.

Conclusions:  In ICS‐treated asthma, eNO reflects clinical activity, PbE and AHR but not eosinophilic airway inflammation. Exhaled NO levels are quantitatively and relationally different in asthmatic subjects treated with ICS and continue to have potential for use as a surrogate of asthma pathophysiology in this group.

OSA is increasingly recognized as a major health problem in developed countries. Obesity is the most common risk factor in OSA and hence, the prevalence of OSA is undoubtedly rising given the epidemic of obesity. Recent data also suggest that OSA is highly associated with the metabolic syndrome, and it is postulated that OSA contributes to cardiometabolic dysfunction, and subsequently vasculopathy.

Current evidence regarding the magnitude of impact on ultimate cardiovascular morbidity or mortality attributable to OSA‐induced metabolic dysregulation is scarce. Given the known pathophysiological triggers of intermittent hypoxia and sleep fragmentation in OSA, the potential mechanisms of OSA–obesity–metabolic syndrome interaction involve sympathetic activation, oxidative stress, inflammation and neurohumoral changes. There is accumulating evidence from human and animal/cell models of intermittent hypoxia to map out these mechanistic pathways.

In spite of support for an independent role of OSA in the contribution towards metabolic dysfunction, a healthy diet and appropriate lifestyle modifications towards better control of metabolic function are equally important as CPAP treatment in the holistic management of OSA.