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Combined Haemophilus influenzae respiratory infection and allergic airways disease drives chronic infection and features of neutrophilic asthma

Background

20–30% of patients with asthma have neutrophilic airway inflammation and reduced responsiveness to steroid therapy. They often have chronic airway bacterial colonisation and Haemophilus influenzae is one of the most commonly isolated bacteria. The relationship between chronic airway colonisation and the development of steroid-resistant neutrophilic asthma is unclear.

 Objectives

To investigate the relationship between H influenzae respiratory infection and neutrophilic asthma using mouse models of infection and ovalbumin (OVA)-induced allergic airways disease.

 Methods

BALB/c mice were intratracheally infected with H influenzae (day 10), intraperitoneally sensitised (day 0) and intranasally challenged (day 12–15) with OVA. Treatment groups were administered dexamethasone intranasally during OVA challenge. Infection, allergic airways disease, steroid sensitivity and immune responses were assessed (days 11, 16 and 21).

 Results

The combination of H influenzae infection and allergic airways disease resulted in chronic lung infection that was detected on days 11, 16 and 21 (21, 26 and 31 days after infection). Neutrophilic allergic airways disease and T helper 17 cell development were induced, which did not require active infection. Importantly, all features of neutrophilic allergic airways disease were steroid resistant. Toll-like receptor 4 expression and activation of phagocytes was reduced, but most significantly the influx and/or development of phagocytosing neutrophils and macrophages into the airways was inhibited.

 Conclusions

The combination of infection and allergic airways disease promotes bacterial persistence, leading to the development of a phenotype similar to steroid-resistant neutrophilic asthma and which may result from dysfunction in innate immune cells. This indicates that targeting bacterial infection in steroid-resistant asthma may have therapeutic benefit.

Allergic rhinitis is associated with poor asthma control in children with asthma

Background

Asthma and allergic rhinitis are the two most common chronic disorders in childhood and adolescence. To date, no study has examined the impact of comorbid allergic rhinitis on asthma control in children.

 Objective

To examine the prevalence of allergic rhinitis in children with asthma, and the impact of the disease and its treatment on asthma control.

 Methods

A cross-sectional survey in 203 children with asthma (5–18 years) using validated questionnaires on rhinitis symptoms (stuffy or runny nose outside a cold) and its treatment, and the paediatric Asthma Control Questionnaire (ACQ). Fraction of nitric oxide in exhaled air (FeNO) was measured with a Niox Mino analyser; total and specific IgE levels were assessed by the Immunocap system.

 Results

157 children (76.2%) had symptoms of allergic rhinitis but only 88 of these (56.1%) had been diagnosed with the condition by a physician. ACQ scores were worse in children with allergic rhinitis than in those without the condition (p=0.012). An ACQ score ≥1.0 (incomplete asthma control) was significantly more likely in children with allergic rhinitis than in those without (OR 2.74, 95% CI 1.28 to 5.91, p=0.0081), also after adjustment for FeNO levels and total serum IgE. After adjustment for nasal corticosteroid therapy, allergic rhinitis was no longer associated with incomplete asthma control (OR 0.72, 95% CI 0.47 to 1.12, p=0.150).

 Conclusion

Allergic rhinitis is common in children with asthma, and has a major impact on asthma control. The authors hypothesise that recognition and treatment of this condition with nasal corticosteroids may improve asthma control in children, but randomised clinical trials are needed to test this hypothesis.

Sex, susceptibility to smoking and chronic obstructive pulmonary disease: the effect of different diagnostic criteria. Analysis of the Health Survey for England

Background

Some previous studies suggest there are sex differences in susceptibility to, and prevalence of, chronic obstructive pulmonary disease (COPD) but findings are inconsistent. In this study, whether different diagnostic criteria for COPD may contribute to these conflicting findings was examined.

 Methods

Cross sectional analysis of data from the 1995, 1996 and 2001 Health Survey for England was undertaken, including participants of white ethnicity, aged 40+ years with a valid smoking history and lung function data. COPD was defined using Global Initiative for Chronic Obstructive Lung Disease (GOLD), National Institute for Health and Clinical Excellence (NICE) and lower limit of normal (LLN) spirometric criteria, in the absence of a diagnosis of asthma.

 Results

COPD was present in 3035 (16.1%), 1304 (7.0%) and 1684 (9.0%) people, according to the GOLD, NICE and LLN criteria, respectively. With both the GOLD and NICE definitions, men had significant independent increased risks of COPD compared with women (OR 1.46 (95% CI 1.34 to 1.59) and 1.30 (1.15 to 1.48), respectively). With the LLN definition, this effect was removed (OR 0.96 (0.87 to 1.07). With the use of both the GOLD and NICE criteria, women had significantly greater susceptibility to COPD (25–30% higher risk) for the same level of pack years of exposure. This was not observed with the LLN criteria.

 Conclusions

The study indicates that sex differences in risk of COPD reported in previous studies are influenced by the definition used for COPD. When using a statistically driven definition (LLN), no independent sex difference was found and there was no evidence of an increased susceptibility to COPD among female compared with male smokers.

CT screening for lung cancer: so near, yet so far

The UK Lung Screen team in their positional statement outlined the issues to be explored by the trial on CT screening for lung cancer.1 Although it seems to be a large, well-planned study, we believe that there are some shortcomings in this study that may undermine its significance. There are several other aspects of CT screening that need to be investigated in order to determine the suitability of the screening and thus guide a national programme. The additional investigation areas may include:

  • Studying the number of unnecessary lung biopsies, invasive procedures and surgeries due to cancer screening and the morbidity and mortality caused by these procedures.

  • The risk of development of radiation-induced malignancy, both in patients undergoing routine yearly screening and in those subjected to serial CT scans for suspicious lesions. Some studies have shown significant risk of development of radiation-induced malignancies.2

  • ...

    • Comparing the American and European diagnostic guidelines for cystic fibrosis: same disease, different language?

    Background

    The American and European cystic fibrosis (CF) guidelines recommend different diagnostic criteria. This study assessed diagnostic concordance between these recommendations.

     Methods

    Subjects with single organ manifestations suggestive of CF (chronic sinopulmonary disease (RESP), chronic/recurrent pancreatitis (PANC) or obstructive azoospermia (AZOOSP)) were prospectively evaluated by sweat test, nasal potential difference and genotyping. Concordance in diagnostic outcomes between the two algorithms was measured using observed agreement and statistics.

     Results

    A total of 208 subjects were evaluated. Observed agreement was 84.8% and level of agreement was excellent (=0.87) between the American and European recommendations. The RESP phenotype was associated with the highest degree of concordance (observed agreement ≥90%, =0.92) compared with the PANC (observed agreement 86%, =0.65) and AZOOSP (observed agreement 80%, =0.87) phenotypes. Incorporation of nasal potential difference into the American algorithm failed to improve the overall degree of concordance (good agreement level; =0.75); the level of agreement was unchanged in RESP and PANC subjects, but reduced in AZOOSP subjects (from excellent to good). Extensive genotyping had limited clinical utility in the diagnosis of CF in both algorithms.

     Conclusions

    Despite inconsistencies between the American and European diagnostic recommendations, concordance in diagnostic outcomes among subjects presenting with single organ manifestations of CF was good to excellent. These diagnostic guidelines provide guidance and promote rigorous evaluation for the diagnosis of CF but neither guideline should be regarded as dogma.

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