Exposing rodents to a combination of tobacco smoke and lipopolysaccharide results in an exaggerated inflammatory response in the lung

BACKGROUND AND PURPOSE

Acute exacerbations of chronic obstructive pulmonary disease (COPD), which are often associated with respiratory infections, are defined as a worsening of symptoms that require a change in medication. Exacerbations are characterized by a reduction in lung function, quality of life and are associated with increased pro-inflammatory mediators in the lung. Our aim was to develop an animal model to mimic aspects of this exaggerated inflammatory response by combining key etiological factors, tobacco smoke (TS) and bacterial lipopolysaccharide (LPS).

EXPERIMENTAL APPROACH

Rats were exposed to TS for 30 min twice a day for 2 days. On day 3 animals were exposed to LPS for 30 min followed by exposure to TS 5 h later. Inflammation, mucus and lung function were assessed 24 h after LPS.

KEY RESULTS

Neutrophils, mucus, oedema and cytotoxicity in lung and/or bronchoalveolar lavage was increased in animals exposed to combined LPS and TS, compared with either stimulus alone. Lung function was impaired in animals exposed to combined LPS and TS. Inflammatory cells, oedema and mucus were unaffected by pretreatment with the corticosteroid, budesonide, but were reduced by the phosphodiesterase 4 selective inhibitor roflumilast. Additionally, lung function was improved by roflumilast.

CONCLUSIONS AND IMPLICATIONS

We have established an in vivo model mimicking characteristic features of acute exacerbations of COPD including lung function decline and increased lung inflammation. This model may be useful to investigate molecular and cellular mechanisms underlying such exacerbations, to identify new targets and to discover novel therapeutic agents.     

Invasive oral aspergillosis in a patient with acute myeloid leukaemia

Aspergillosis (a fungal infection by an organism of the Aspergillus species) of the oral cavity is an uncommon condition which most frequently occurs in immunocompromised patients, such as those with haematological malignancies. In such patients, prolonged neutropenia secondary to chemotherapeutic agents enables the spread of invasive aspergillosis, which is unaffected by anatomical barriers. Early detection and treatment of the condition is essential to avoid more serious complications, such as disseminated infection, which results in increased morbidity and mortality. This case report describes a patient with acute myeloid leukaemia who developed localized invasive Aspergillus flavus of the palate. High‐dose antifungal therapy was instituted along with surgical removal of the involved tissues. Aspergillosis of the palate was successfully eradicated with no long‐term ill effects from the treatment. Management of invasive aspergillosis includes early aggressive antifungal medication combined with surgical removal of the involved tissues.     

Association between falls and high-risk medication use in hospitalized Asian elderly patients

Aim:   Most studies looking at the relation between medication use and fall among the hospitalized elderly patients, were done in Western countries. So, a study was planned to investigate the role of medications in causing falls in hospitalized Asian elderly patients.
Methods:   Case note review was done for all patients age 65 years and above, who fell at least once during their hospital stay over a 12-month period. Information obtained from the case notes included: (i) demographic information; (ii) Modified Morse Fall scale; (iii) circumstances and time of fall; and (iv) medication use. From the hospital admission database, an age- and sex-matched control group was selected for comparison.
Results:   Over the 12-month study period, 298 patients met the study criteria. Average age of the patients was 75.8 years, 60.4% were male and 84.9% were Chinese. Multivariate analysis showed that fallers had longer lengths of stay and were more likely to have a history of falls. Fallers were also more likely to be taking hypnotics, cough preparations and anti-platelets, but less likely to be taking paracetamol. Fallers were on fewer medications.
Conclusion:   Elderly hospitalized patients on hypnotic drugs, cough preparations and anti-platelets were more likely to fall. Appropriate usage of analgesics, especially paracetamol, to relieve pain may reduce falls.     

Effects of inhaled corticosteroid on bone turnover in children with bronchial asthma

Long-term usage of systemic steroids is associated with multiple side effects. One of the major morbidities is due to its effect on bone metabolism leading to bone loss and resulting in skeletal fractures. This study was conducted to determine the effects of inhaled steroids on bone mineral density (BMD) and biochemical bone markers. Twenty-four children with frequent episodic or mild persistent asthma who satisfied the clinical criteria for starting on inhaled corticosteroids (ICS) were enrolled into the study. The BMD scan was done using dual energy X-ray absorptiometry, prior to starting ICS therapy and 6 months later. Biochemical markers of bone metabolism, (i) serum osteocalcin as a bone formation marker, and (ii) urinary deoxypyridinoline (Upd) as a bone resorption marker, were taken prior to ICS treatment and at 2 monthly intervals. The biochemical markers were all taken in the morning. Twenty-four, age- and sex-matched children with mild episodic asthma, not requiring ICS, were used as controls for the BMD measurements. The BMD scan was done upon enrollment into the study and 6 months later. Twenty-four children on ICS and 24 controls completed the study. The subjects were on a mean dose of beclomethasone dipropionate (BDP) 0.4 mg/day. One subject needed a short course of Prednisolone in the early treatment period. None of the controls needed oral steroid therapy. One child in the control group sustained a greenstick fracture after an accidental fall. The mean rate of change of BMD was 1.8% +/- 12.3 in the subjects on BDP. This was lower than the 6.1% +/- 10.6 among the control subjects. However, this difference did not reach statistical significance (P = 0.16). There was a significant increase in serum osteocalcin level after 6 months of BDP treatment from 66.83 +/- 22.71 ng/mL to 81.61 +/- 24.66 ng/mL (P < 0.005). There was a decline in Upd from 36.2 +/- 47.1 nmol/mmol creatinine to 21.4 +/- 6.92 nmol/mmol creatinine. However, this did not reach statistical significance. There was no difference in the statural gain between the subjects on ICS and their controls. This study showed that 6 months of ICS therapy (mean dose 0.4 mg/day) had no significant adverse effect on bone metabolism in asthmatic children.     

Protocol for: Sheffield Obesity Trial (SHOT): A randomised controlled trial of exercise therapy and mental health outcomes in obese adolescents [ISRCNT83888112]

Background  

While obesity is known to have many physiological consequences, the psychopathology of this condition has not featured prominently in the literature. Cross-sectional studies have indicated that obese children have increased odds of experiencing poor quality of life and mental health. However, very limited trial evidence has examined the efficacy of exercise therapy for enhancing mental health outcomes in obese children, and the Sheffield Obesity Trial (SHOT) will provide evidence of the efficacy of supervised exercise therapy in obese young people aged 11–16 years versus usual care and an attention-control intervention.     

Modulation of the peripheral T-Cell response by CD4 mutants of hepatitis C virus: transition from a Th1 to a Th2 response

A disturbing feature of hepatitis C virus (HCV) is its long-term persistence in roughly 85% of those infected. Escape mutants may play a major role in HCV persistence. Our previous studies have identified a human leukocyte antigen DRB1*15 (HLA-DRB1*15) restricted Th1 epitope in the HCV NS3 protein, NS3(358-375), and escape variants of this epitope that may emerge under immune selection. Such variants attenuate or fail to stimulate T-cell proliferation. Here we provide data from peripheral blood mononuclear cells derived from four HLA-DRB1*15 patients chronically infected with HCV, and report that naturally occurring single amino acid substitutions in the Th1 epitope NS3(358-375) fail to stimulate proliferation, which is accompanied by a shift in cytokine secretion patterns from one characteristic of a Th1 antiviral responses to a Th2 form. Further, in one patient, we demonstrate that HCV variant peptides can effectively inhibit host polyclonal peripheral T-cell proliferation. We speculate that this phenomenon may be a factor in chronic HCV infection.