Characterising the Microbiota in Asthma

The main aim of this project is to determine if microbiota composition is correlated with disease severity (as determined by BTS step). Although initial studies suggest that asthmatics of different severities may have similar microbiota composition, there is no direct evidence to support this assertion. Also, the three main studies in this area so far have all used different sequencing methods, making comparisons difficult.

The relationship between the microbiota composition of different subjects and clinical measures including bronchial hyperreactivity (as measured by methacholine challenge) and pattern of airway inflammation (as measured by sputum differential cell count and exhaled nitric oxide levels) will be investigated further. Comparisons will also be made between samples from asthmatic patients using the inhaled steroid fluticasone and those using budesonide, as there is evidence suggesting that fluticasone leads to an increased risk of pneumonia and non tuberculous mycobacterial disease in certain patient groups. Unpublished data (Astra Zeneca) suggests the excess risk of pneumonia with fluticasone compared to budesonide may be more pronounced after at least 12 months of treatment with inhaled corticosteroid. Microbiota composition of the sputum samples will be evaluated in conjunction with standard microbiological culture of these samples to allow a comparison between these two methods.

In order to assess the reproducibility of the induced sputum method for assessing the lung microbiota, a repeat sputum sample will be taken from a subgroup of 20 patients within 24 hours of the collection of the first sample and compared. A further sample will be taken from this subgroup of patients 2 weeks later to assess the longitudinal stability of the bacterial population.

Inclusion criteria

• Age 18 or above
• Male or female
• Diagnosis of asthma
• Non-smokers for 10 years and <10 pack year equivalents in total
• BTS Step 2 patients must have been using inhaled steroids at a dose of BDP ≤ 400 mcg/day FP ≤ 200 mcg/day or BUD ≤ 400 mcg/day for at least 1 year
• BTS Step 4 patients must have been using inhaled steroids at a dose of FP ≥ 500 mcg/day or BUD ≥800 mcg/day for at least 1 year as a separate steroid or inhaled steroid/long acting beta agonist combination.

Exclusion criteria

• Respiratory infection or antibiotics within last month
• Pregnancy or intent to become pregnant during course of study
• Other respiratory diagnosis
• Post bronchodilator FEV1 of < 60%