Viruses in bronchiectasis: a pilot study to explore the presence of community acquired respiratory viruses in stable patients and during acute exacerbations.

BACKGROUND: Bronchiectasis is a chronic respiratory condition. Persistent bacterial colonisation in the stable state with increased and sometimes altered bacterial burden during exacerbations are accepted as key features in the pathophysiology. The extent to which respiratory viruses are present during stable periods and in exacerbations is less well understood. METHODS: This study aimed to determine the incidence of respiratory viruses within a cohort of bronchiectasis patients with acute exacerbations at a teaching hospital and, separately, in a group of patients with stable bronchiectasis. In the group of stable patients, a panel of respiratory viruses were assayed for using real time quantitative PCR in respiratory secretions and exhaled breath. The Impact of virus detection on exacerbation rates and development of symptomatic infection was evaluated. RESULTS: Routine hospital-based viral PCR testing was only requested in 28% of admissions for an exacerbation. In our cohort of stable bronchiectasis patients, viruses were detected in 92% of patients during the winter season, and 33% of patients during the summer season. In the 2-month follow up period, 2 of 27 patients presented with an exacerbation. CONCLUSIONS: This pilot study demonstrated that respiratory viruses are commonly detected in patients with stable bronchiectasis. They are frequently detected during asymptomatic viral periods, and multiple viruses are often present concurrently.

The impact of severe lung disease on evidential breath analysis collection.

BACKGROUND: It is a legal requirement to supply a breath analysis sample when requested by Police at roadside checkpoints. The current device requires a 1L sample at 8L·min(-1). Court disputes commonly attribute respiratory disease for failure to produce a sample. OBJECTIVE: To determine whether respiratory disease aetiology and/or severity precludes an adequate breath sample using a modern evidential breath analyser. METHODS: Subjects performed breath analysis following standard Police procedure. Three efforts within 15min were allowed and any reasons for failure recorded. RESULTS: 24 subjects with interstitial lung disease (ILD) and 26 subjects with chronic obstructive pulmonary disease (COPD) were studied and met minimum respiratory function criteria as per device specifications. 18 ILD subjects (75%) and 24 COPD subjects (92%) were able to provide a sample. All subjects with a vital capacity below 1.5L were unable to provide a sample. DISCUSSION: In the balance of probabilities most patients with lung disease are able to supply an evidential breath sample. The exception is a very severe disease, particularly in volume limited patients.

Exercise-Induced Bronchoconstriction Identified Using the Forced Oscillation Technique.

Objective: Lung mechanics using the forced oscillation technique (FOT) is suggested to be equivalent and more sensitive in determining exercise-induced bronchoconstriction (EIB) than spirometry. Dynamic alterations in minute ventilation (VE) may affect this measurement. We investigated changes in FOT parameters post exercise challenge (EC) in people with asthma as compared to spirometry. The rate of recovery and any effect of raised VE following exercise on FOT parameters were also assessed. Method: Airway resistance (R5) and reactance (X5) at 5 Hz and VE were measured prior to forced expiratory volume in 1 s (FEV1) before and up to 20 min after a standard EC in people with asthma and healthy controls. Airway hyperresponsiveness to the hyperosmolar mannitol test was measured in the asthmatic subjects within 1 week of the EC. Baseline and sequential measures were assessed using repeated measures ANOVA and Pearson's correlation. Group demographics and recovery data were compared using an unpaired t test. Results: Subjects with current asthma (n = 19, mean ± SD age 28 ± 6 years) and controls (n = 10, 31 ± 5 years) were studied. Baseline FEV1, R5, X5, and VE were similar between groups (p > 0.09). Airway hyperresponsiveness was present in 12/19 asthmatic subjects. The EC max % change of R5 and X5 correlated with FEV1 (r > 0.90) and were only different to controls in those with asthma that responded by FEV1 criteria (p < 0.01). EC recovery of R5 was similar to FEV1; however, X5 was greater (p = 0.03). Elevated VE post EC did not affect the % change in FOT parameters across all subjects (p > 0.3). R5 and X5 were highly sensitive in determining a positive EC response (80-86%), but X5 was more specific (93 vs. 80%). Conclusion: FOT parameters tracked with forced maneuvers and were not influenced by increased ventilation following an exercise challenge designed to elicit EIB. FOT identified EIB similarly to spirometry in patients with asthma.

Exercise-induced Bronchoconstriction with Firefighting Contained Breathing Apparatus.

PURPOSE: Protective self-contained breathing apparatus (SCBA) used for firefighting delivers decompressed (cold) dehumidified air that may enhance the severity of exercise-induced bronchoconstriction (EIB) in those susceptible. We investigated the effect of SCBA during exercise on airway caliber in people with asthma and healthy controls. METHODS: Two exercise challenges (EC) designed to elicit EIB were performed on separate days within 1 wk. The initial challenge was breathing room air (ECRA) with workload titrated to elicit >60% estimated maximum voluntary ventilation. The exercise intensity was repeated for the second challenge using SCBA (ECSCBA). Forced expiratory volume in 1 s (FEV1) was measured before and up to 20 min after exercise. Bronchial hyperresponsivenss (BHR) to the hyperosmolar mannitol test was measured in the subjects with asthma. RESULTS: Twenty subjects with current asthma (mean [SD]: age 27 [6] yr) and 10 healthy controls (31 [5] yr, P = 0.1) were studied. The percent fall in FEV1 after ECSCBA was greater in the mannitol-positive asthma subjects (14.4% [15.1%]) compared with mannitol-negative asthmatic subjects (1.6% [1.7%]; P = 0.02) and controls (2.3% [2.3%]; P = 0.04). The FEV1 response was not different between ECRA and ECSCBA (0.49% [5.57%]; P = 0.6). No BHR to mannitol (n = 7) was highly sensitive for identifying a negative response to ECSCBA (negative predictive value 100%). CONCLUSIONS: The SCBA does not increase the propensity or severity for EIB in subjects with BHR. Those subjects with asthma but no BHR to inhaled mannitol did not exhibit EIB. The BHR to a hyperosmolar stimulus maybe considered a useful screening tool for potential recruits with a history of asthma.

Spirometry filters can be used to detect exhaled respiratory viruses.

Respiratory viruses are very common in the community and contribute to the burden of illness for patients with chronic respiratory diseases, including acute exacerbations. Traditional sampling methods are invasive and problematic to repeat. Accordingly, we explored whether respiratory viruses could be isolated from disposable spirometry filters and whether detection of viruses in this context represented presence in the upper or lower respiratory tract. Discovery (n = 53) and validation (n = 49) cohorts were recruited from a hospital outpatient department during two different time periods. Spirometry mouthpiece filters were collected from all participants. Respiratory secretions were sampled from the upper and lower respiratory tract by nasal washing (NW), sputum, and bronchoalveolar lavage (BAL). All samples were examined using RT-PCR to identify a panel of respiratory viruses (rhinovirus, respiratory syncytial virus, influenza A, influenza B, parainfluenza virus 1, 2 & 3, and human metapneumovirus). Rhinovirus was quantified using qPCR. Paired filter-NW samples (n = 29), filter-sputum samples (n = 24), filter-BAL samples (n = 39) and filter-NW-BAL samples (n = 10) provided a range of comparisons. At least one virus was detected in any sample in 85% of participants in the discovery cohort versus 45% in the validation cohort. Overall, 72% of viruses identified in the paired comparator method matched those detected in spirometry filters. There was a high correlation between viruses identified in spirometry filters compared with viruses identified in both the upper and lower respiratory tract using traditional sampling methods. Our results suggest that examination of spirometry filters may be a novel and inexpensive sampling method for the presence of respiratory viruses in exhaled breath.

Combined inhaled salbutamol and mannitol therapy for mucus hyper-secretion in pulmonary diseases.

This study focuses on the co-engineering of salbutamol sulphate (SS), a common bronchodilator, and mannitol (MA), a mucolytic, as a potential combination therapy for mucus hypersecretion. This combination was chosen to have a synergic effect on the airways: the SS will act on the ß2-receptor for relaxation of smooth muscle and enhancement of ciliary beat frequency, whilst mannitol will improve the fluidity of mucus, consequently enhancing its clearance from the lung. A series of co-spray-dried samples, containing therapeutically relevant doses of SS and MA, were prepared. The physico-chemical characteristics of the formulations were evaluated in terms of size distribution, morphology, thermal and moisture response and aerosol performance. Additionally, the formulations were evaluated for their effects on cell viability and transport across air interface Calu-3 bronchial epithelial cells, contractibility effects on bronchial smooth muscle cells and cilia beat activity using ciliated nasal epithelial cells in vitro. The formulations demonstrated size distributions and aerosol performance suitable for inhalation therapy. Transport studies revealed that the MA component of the formulation enhanced penetration of SS across the complex mucus layer and the lung epithelia cells. Furthermore, the formulation in the ratios of SS 10(-6) and MA 10(-3) M gave a significant increase in cilia beat frequency whilst simultaneously preventing smooth muscle contraction associated with mannitol administration. These studies have established that co-spray dried combination formulations of MA and SS can be successfully prepared with limited toxicity, good aerosol performance and the ability to increase ciliary beat frequency for improving the mucociliary clearance in patients suffering from hyper-secretory diseases, whilst simultaneously acting on the underlying smooth muscle.