Bronchiectasis in the Last Five Years: New Developments
It meant the Acapella did not have to be used separately after the Albuterol and shortened total therapy time. The hospital nebulizer system was much faster than my home machine, which can take 20 or more minutes to breathe the Albuterol. The quickness was wonderful and would make consistent use much better. Are there any really fast nebulizers on the market? We agree, this device is much faster than other systems.
We are not sure of anything faster at the moment. My nebulizer is so slow, compared to the hospital system. It takes about 20 minutes per treatment and adding the Acapella adds a huge amount of time to a morning routine Since my Bronchictisis is not severe, I tend to skip, doing it once in the evening instead of twice daily.
The Aerobika device is wonderful and I am lucky to have gotten it through a hospital stay for surgery because it is expensive. While demonstrating promise, lung microbiome analysis currently remains a research tool, and further trials are required and underway to assess its clinical relevance [ 18 ] and utility, especially in assessing early antibiotic resistance. Similar to other airway disorders such as asthma and COPD, there is an increasing body of literature, suggesting that phenotyping patients by combining clinical, radiological, inflammatory, and microbiological characteristics allows identification of those individuals that have a more rapid disease progression or exacerbate frequently [ 23 ].
Aliberti and colleagues described four phenotypic clusters based primarily on microbiological analysis the presence of P. They found that those with infection Clusters 1 and 2 had significantly more exacerbations, poorer lung function, poorer quality of life as measured by the St. One-year mortality was similar in all groups, but three-year mortality was significantly higher in the P. Mortality was lower in the younger cohort of patients 16 deaths over five years in Clusters 1 and 2 compared with the older group with either frequent exacerbations or more severe disease 76 deaths over five years in Clusters 3 and 4.
Further research needs to be undertaken in identifying phenotypes within other global populations, and especially within indigenous populations where the morbidity and mortality is disproportionately increased. From such research, some unifying characteristics allowing standardisation of clinical phenotypes globally in bronchiectasis might emerge. Bronchiectasis is associated with neutrophilic airway inflammation as measured by sputum and bronchoalveolar lavage differential cell counts, and neutrophil-specific by-products such as blood and sputum interleukin-8 and neutrophil elastase.
Recent studies have identified specific profiles of mucins proteins secreted by airway epithelium and found in sputum , airway disorders such as COPD, and bronchiectasis, with high levels of MUC2 gene found in the latter condition [ 25 , 26 ]. Mucins described in bronchiectasis MUC2 may reflect bacterial load and P. The reverse, namely, the prevalence of clinical and radiological smoking-related COPD in patients with a primary diagnosis of bronchiectasis is low.
- The Guardian Code: Its Not Your Fault [And I Can Prove It!].
- Non-CF Bronchiectasis Patients Show Improvement with Aerobika Device;
- Cattle King For The A Day (Stories from the Golden Age).
- Daring the Devil--spiritual warfare.
- The Fictioneer (1).
- El Cuarto Poder (Spanish Edition);
Recent systematic reviews estimate the occurrence of COPD in patients with a predominant diagnosis of bronchiectasis between 3. Recent literature suggests that asthma coexisting with bronchiectasis is also associated with more frequent exacerbations compared with bronchiectasis alone Mao and colleagues found that patients with bronchiectasis and asthma had a 2. However, the effects of ACOS and bronchiectasis coexisting, in terms of disease progression and exacerbation rates are unknown, and more research is required. In the last two years, questionnaires have been developed and validated in bronchiectasis to assess disease-specific quality of life and disease severity.
For each scale, scores are between 1 and Higher scores indicate better health-related quality of life. Thresholds for a clinically significant change in health status using QOL-B have been established [ 32 ]. Two scores have been developed to assess bronchiectasis severity Table 1: Both have been validated and include clinical, radiological, sputum microbiology and spirometric criteria; specifically age, FEV 1 percent predicted, radiological extent of bronchiectasis, P. The BSI also evaluates Body Mass Index, previous hospitalisation with an exacerbation, and the number of exacerbations in previous year.
Both scores accurately predicted five-year mortality AUC 0. Further studies are required to assess responsiveness to interventions. Forced expiratory volume in 1 s; MRC: Over the last five years, there has been a recognition that clinicians and researchers need to work collaboratively to progress the understanding of the pathophysiology of bronchiectasis and develop new treatments for this disorder.
To that end, a number of collaborative initiatives have been established. It aims to enrol 10, patients with non-CF bronchiectasis throughout Europe over the next five years and to follow them longitudinally. Baseline data and annual follow-up data will be collected on demographics, co-morbidities, aetiology, medications, microbiology, exacerbations, and health utilisation.
The severity, prognosis, and survival of bronchiectasis will be ascertained.
It will also provide a means of trialling new treatments. Similar registries have been initiated in other countries including America in and Australia in Clearance of sputum actively using ACTs is advocated and regularly implemented to reduce the risk of exacerbations in bronchiectasis. Techniques include postural drainage, an active cycle of breathing and other selected breathing manoeuvres, positive expiratory pressure devices, airway oscillating devices, and high-frequency chest wall oscillation.
There is, however, little objective evidence documenting the benefit of ACTs with a Cochrane collaboration finding seven small sample size of less than 30 participants and short-term less than or equal to six months randomised, predominantly crossover, studies in the area. As these studies were heterogeneous, data could not be pooled. Nevertheless, the studies indicated that ACTs either alone or in combination were safe and had a minor and variably significant benefit on symptoms, quality of life, lung function, and sputum clearance [ 37 ].
Large randomised controlled studies of longer duration are required to determine the effect of ACTs on clinically relevant outcomes, such as frequency of exacerbations and antibiotic use [ 37 ]. These clinically significant improvements were noted immediately following the intervention but were not sustained at six months. Fewer exacerbations over 12 months were noted with regular exercise median, 2 vs. A major advance in the management of bronchiectasis is the use of prophylactic macrolide therapy to prevent exacerbations via antibacterial and anti-inflammatory immunomodulatory pathways [ 39 ].
Type of macrolide used, dose, and duration of therapy varies amongst studies, making direct comparisons difficult. Although the number of exacerbations are significantly reduced in patients maintained on macrolides, the number of patients with severe exacerbation requiring admission into hospital is not significantly reduced [ 43 ]. The beneficial effect of macrolides on lung function and health-related quality of life measures St. Significantly increased adverse events with macrolides compared to a placebo include diarrhoea and abdominal discomfort [ 43 ]. Other common antibiotic side effects of nausea or vomiting, headache, and rash are not significantly increased.
There has been a theoretical risk of cardiac arrhythmias and cardiac arrest and sensorineural hearing loss given the class effect of macrolides on prolongation of the QT interval and ototoxicity. However, increased frequency of these adverse effects compared to the placebo has not been noted in the studies to date [ 40 , 41 , 42 ]. Only the BAT trial systematically examined the adverse event of auditory decline based on self-reported hearing impairment or tinnitus. There was no difference between azithromycin and placebo groups [ 41 ].
The BLESS trial examined cardiac events and did not demonstrate a significant difference in the QTc interval or any new cardiac arrhythmia between erythromycin and placebo groups [ 42 ]. In , Ray and colleagues retrospectively reviewed azithromycin use and the risk of cardiovascular death in an American Tennessee cohort of patients who were prescribed azithromycin , prescriptions.
They were matched to those not on antibiotics and to patients who were prescribed amoxicillin, ciprofloxacin, or levofloxacin [ 47 ]. The authors found a significantly increased risk of cardiovascular death with five days of treatment with azithromycin compared with the placebo hazard ratio: Since then, several studies have re-visited this issue and have suggested the actual risk is lower. A Danish cohort study found an increase in the risk of death with azithromycin when compared with the placebo rate ratio RR: A literature review of published studies to found that arrhythmogenicity was related to macrolide concentration in the blood, with oral dosing posing a low risk [ 49 ].
The incidence of arrhythmias and death with macrolides in the absence of underlying risk factors such as QT prolongation and cardiac comorbidities is low [ 49 , 50 ]. Nevertheless, a baseline ECG to assess QT prolongation prior to commencing macrolides is easy to acquire and is recommended. The major concern with prophylactic macrolide use is the evolution of macrolide resistance [ 51 ]. Despite concerns regarding macrolide resistance, it is unclear if microbiological macrolide resistance translates into adverse clinical outcomes. The current clinical consensus is to consider prophylactic antibiotics in those patients with frequent 3 or more exacerbations within the preceding year who have failed standard therapies [ 2 , 53 ].
The role of prophylactic inhaled antibiotics in non-CF bronchiectasis is evolving with the aim of delivering the drug directly into airway to improve antibacterial efficacy and to reduce systemic side effects. These inhaled antibiotics have collectively demonstrated a reduction in sputum bacterial load; their effectiveness on clinical outcomes are awaited [ 54 ].
No improvement was noted in lung function. Earlier studies with mg of nebulised inhaled tobramycin given twice daily from 30 days for up to six months have demonstrated similar findings with a reduction in bacterial density in patients colonised with P. Colistin, a polypeptide antibiotic effective against Gram-negative Bacilli, has demonstrated similar results. The primary endpoint, median time to the first exacerbation, was similar in both groups by an intention to treat analysis 42 vs.
It was, however, increased in those adherent to therapy days in the colistin group vs. Quality of life scores measured by the SGRQ improved significantly by Bacterial growth, however, returned once the active drug was stopped [ 60 ]. This has led to recent studies trialling cyclical inhaled antibiotics with alternative modes of antibiotic delivery to ensure bacterial suppression without an increase in bacterial resistance in chronic lung disease. To that end, antibiotic nanoparticles nano-antibiotics or antibiotics encapsulated into liposomes a minute spherical sac of phospholipid molecules and polymer nanoparticles as carriers are emerging as a new therapy to treat Pseudomonal infections.
These antibiotics, through their encapsulation, theoretically penetrate through mucus and deposit deeper into the lungs. This returned to baseline off treatment, compared with the placebo. Time to first exacerbation also increased vs. Building on this, the Phase 3 studies ORBIT 3 and 4 with inhaled cyclical ciprofloxacin comprised of a mixture of liposome encapsulated and unencapsulated ciprofloxacin have just been completed.
The primary outcome is the time to first pulmonary exacerbation with secondary outcomes including exacerbation frequency and improvement in the quality of life measures. Results are anticipated towards the end of The primary outcome was clinical: This did not achieve clinical nor statistical significance and exacerbation frequency was not reduced. In both studies, adverse effects of dyspnoea, cough, and increased sputum production were significantly increased in the treatment arm [ 63 ]. Further studies are needed to examine the optimum duration of inhaled antibiotics, cyclicity, and their effectiveness in improving clinical outcomes.
Inhaled hyperosmolar agents include hypertonic saline and mannitol, which, with their high osmolarity, mechanistically draw fluid and mucus into the airway-enhancing clearance. Small trials have shown equivocal benefit with hypertonic saline on clinical outcomes, such as exacerbation rate, quality of life, and lung function, and larger studies are required [ 64 ].
Inhaled mannitol at mg twice daily given for one year in patients did not reduce exacerbation rate, the primary outcome, compared with the control group. A small improvement was noted in secondary outcome measures, increased time to first exacerbation HR 0. The role of mannitol is thus currently limited to selected patients. A Cochrane review recently updated its established appraisal of mucolytic therapy in bronchiectasis. No recent studies were found, and the four studies previously included were heterogeneous, precluding a meaningful cohesive analysis [ 66 ].
Nevertheless, ingested bromohexine and erdosteine in small studies improved sputum clearance with variable improvements in lung function, and larger trials are warranted. Inhaled recombitant human deoxyribonuclease RhDNase increases frequency of exacerbations and worsens lung function in non-CF bronchiectasis and should be avoided [ 66 ]. Neutrophil elastase NE , a protease released by neutrophils in bronchiectasis as part of the inflammatory response contributes to airway and lung parenchymal damage and mucus secretion.
Inhibiting neutrophil elastase may potentially dampen the neutrophilic inflammatory response and reduce exacerbations, improving symptoms and lung function in patients with bronchiectasis. In a Phase 2 randomised, double-blind placebo-controlled, parallel group, signal-searching study, Stockley and colleagues investigated the efficacy and safety of AZD NE inhibitor at 60 mg twice daily over four weeks in 38 patients [ 67 ].
Bronchiectasis in the Last Five Years: New Developments
The baseline characteristics of the groups were not entirely matched. Although these devices look different, most work in a similar way. Generally, they use a combination of vibrations and air pressure to make it easier to cough out any mucus. But these devices aren't always available on the NHS, so you may have to pay for one yourself. Occasionally, medication inhaled through a device called a nebuliser may be recommended to help make it easier for you to clear your lungs. Nebulisers are devices consisting of a face mask or mouthpiece, a chamber to convert the medication into a fine mist, and a compressor to pump the medication into your lungs.
A number of different medications can be administered using a nebuliser, including salt water solutions. These medications help reduce the thickness of your phlegm so it's easier to cough it out. Nebulisers can also be used to administer antibiotics, if necessary. But while the medications used with a nebuliser can be provided on prescription, the nebuliser device itself isn't always available on the NHS.
In some areas, a local respiratory service may provide the device without charge, but if this isn't an option, you may have to pay for a device. If you have a particularly severe flare-up of symptoms, you may be prescribed bronchodilator medications on a short-term basis. Bronchodilators are inhaled medications that help make breathing easier by relaxing the muscles in the lungs. Examples of this type of medication include beta 2-adrenergic agonist, anticholinergics and theophylline.