Acute Respiratory Exacerbations Research Articles

Microbial composition in the nose of children with and without viruses during asthma exacerbations.

Recent evidence suggests microbial composition of the respiratory tract can influence respiratory health and disease. We sought to further elucidate the role of microbial communities in the upper respiratory tract during acute respiratory viral infections and exacerbations of asthma in a pediatric population. We recruited 155 children, ages 4-18 years, during asthma exacerbations (AE) (n=97) or during cold symptoms (CS) without history of asthma (n=58) from the emergency department over 4 years. A nasopharyngeal swab was obtained to provide both RNA for virus identification by viral genome sequencing and DNA for microbial composition by 16S rRNA gene sequencing. LEfSe analysis was performed to determine differences in relative contribution between microbial communities within and between groups. Subjects with AE and viral infection were found to have more abundant communities of Pseudomonadales (Moraxellaceae) (LDA score 5; p<0.05), while those AE without virus were found to have more Bifidobacteriacea (LDA 3; p<0.05). Heat maps of bacterial communities clustered by weighted UniFrac suggest microbial composition initially separates between AE and CS cohorts. However, viral detection noticeably alters the microbial composition and further separates each cohort into those with and without infection. In our pediatric population, the bacterial family Moraxellaceae was most related to AE during viral infections. Furthermore, viral infection was associated with compositional shifts of the microbiota within each cohort (AE and CS). Taken together, our data suggests AEs are increased during a viral infection that happens concurrently with an upper-respiratory tract that is composed of specific bacterial communities, such as Moraxellaceae.

Lung inflammatory environments differentially alter mesenchymal stromal cell behavior.

Mesenchymal stromal (stem) cells (MSCs) are increasingly demonstrated to ameliorate experimentally induced lung injuries through disease-specific anti-inflammatory actions, thus suggesting that different in vivo inflammatory environments can influence MSC actions. To determine the effects of different representative inflammatory lung conditions, human bone marrow–derived MSCs (hMSCs) were exposed to in vitro culture conditions from bronchoalveolar lavage fluid (BALF) samples obtained from patients with either the acute respiratory distress syndrome (ARDS) or with other lung diseases including acute respiratory exacerbations of cystic fibrosis (CF) (non-ARDS). hMSCs were subsequently assessed for time- and BALF concentration–dependent effects on mRNA expression of selected pro- and anti-inflammatory mediators, and for overall patterns of gene and mRNA expression. Both common and disease-specific patterns were observed in gene expression of different hMSC mediators, notably interleukin (IL)-6. Conditioned media obtained from non-ARDS BALF-exposed hMSCs was more effective in promoting an anti-inflammatory phenotype in monocytes than was conditioned media from ARDS BALF-exposed hMSCs. Neutralizing IL-6 in the conditioned media promoted generation of anti-inflammatory monocyte phenotype. This proof of concept study suggest that different lung inflammatory environments potentially can alter hMSC behaviors. Further identification of these interactions and the driving mechanisms may influence clinical use of MSCs for treating lung diseases.

Duration of intravenous antibiotic therapy in people with cystic fibrosis.

Progressive lung damage from recurrent exacerbations is the major cause of mortality and morbidity in cystic fibrosis. Life expectancy of people with cystic fibrosis has increased dramatically in the last 40 years. One of the major reasons for this increase is the mounting use of antibiotics to treat chest exacerbations caused by bacterial infections. The optimal duration of intravenous antibiotic therapy is not clearly defined. Individuals usually receive intravenous antibiotics for 14 days, but treatment may range from 10 to 21 days. A shorter duration of antibiotic treatment risks inadequate clearance of infection which could lead to further lung damage. Prolonged courses of intravenous antibiotics are expensive and inconvenient. The risk of systemic side effects such as allergic reactions to antibiotics also increases with prolonged courses and the use of aminoglycosides requires frequent monitoring to minimise some of their side effects. However, some organisms which infect people with cystic fibrosis are known to be multi-resistant to antibiotics, and may require a longer course of treatment. This is an update of previously published reviews. To assess the optimal duration of intravenous antibiotic therapy for treating chest exacerbations in people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals, abstract books and conference proceedings. Most recent search of the Group's Cystic Fibrosis Trials Register: 30 May 2019.We also searched online trials registries. Most recent search of the ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP) portal: 06 January 2019. Randomised and quasi-randomised controlled trials comparing different durations of intravenous antibiotic courses for acute respiratory exacerbations in people with CF, either with the same drugs at the same dosage, the same drugs at a different dosage or frequency or different antibiotics altogether, including studies with additional therapeutic agents. No eligible trials were identified for inclusion. A trial looking at the standardised treatment of pulmonary exacerbations is currently ongoing and will be included when the results are published. MAIN RESULTS: No eligible trials were included. There are no clear guidelines on the optimum duration of intravenous antibiotic treatment. Duration of treatment is currently based on unit policies and response to treatment. Shorter duration of treatment should improve quality of life and adherence, result in a reduced incidence of drug reactions and be less costly. However, the shorter duration may not be sufficient to clear a chest infection and may result in an early recurrence of an exacerbation. This systematic review identifies the need for a multicentre, randomised controlled trial comparing different durations of intravenous antibiotic treatment as it has important clinical and financial implications. The currently ongoing STOP2 trial is expected to provide some guidance on these questions when published.

Association Between Transient Opioid Use and Short-Term Respiratory Exacerbation Among Adults With Chronic Obstructive Pulmonary Disease: A Case-Crossover Study.

The association of historical opioid use with health care use and death among patients with chronic obstructive pulmonary disease (COPD) has been tested. Using Mississippi Medicaid data, we examined the association of transient or short-term opioid use and acute respiratory exacerbations among adults with COPD. We used a case-crossover design and 2013-2017 Mississippi Medicaid administrative claims data. A total of 1,972 qualifying exacerbation events occurred in 1,354 beneficiaries. The frequency and dose of opioid exposure in the 7 days before the exacerbation were examined and compared with the opioid exposure in 10 control windows, each 7 days long, before the exacerbation. Adjusted odds ratios were estimated using conditional logistic regression models to estimate the risk of opioid use on exacerbations after accounting for use of bronchodilators, corticosteroids, benzodiazepines, and β-blockers. Overall, opioid exposure in the 7 days before an exacerbation was significantly associated with acute respiratory exacerbation (odds ratio = 1.81; 95% confidence interval: 1.60, 2.05). Each 25-mg increase in morphine equivalent daily dose was associated with an 11.2% increase in the odds of an acute respiratory exacerbation (odds ratio = 1.11; 95% confidence interval: 1.04, 1.20). Transient use of opioids was significantly associated with acute respiratory exacerbation of COPD.

Efficacy of oral amoxicillin–clavulanate or azithromycin for non-severe respiratory exacerbations in children with bronchiectasis (BEST-1): a multicentre, three-arm, double-blind, randomised placebo-controlled trial

SummaryBackgroundBronchiectasis guidelines recommend antibiotics for the treatment of acute respiratory exacerbations, but randomised placebo-controlled trials in children are lacking. We hypothesised that oral amoxicillin–clavulanate and azithromycin would each be superior to placebo in achieving symptom resolution of non-severe exacerbations in children by day 14 of treatment.MethodsIn this multicentre, three-arm, parallel, double-dummy, double-blind, randomised placebo-controlled trial at four paediatric centres in Australia and New Zealand, we enrolled children aged 1–18 years with CT-confirmed bronchiectasis unrelated to cystic fibrosis, who were under the care of a respiratory physician and who had had at least two respiratory exacerbations in the 18 months before study entry. Participants were allocated (1:1:1) at exacerbation onset to receive oral suspensions of amoxicillin–clavulanate (45 mg/kg per day) plus placebo azithromycin, azithromycin (5 mg/kg per day) plus placebo amoxicillin–clavulanate, or both placebos for 14 days. An independent statistician prepared a computer-generated, permuted-block (size 2–8) randomisation sequence, stratified by centre, age, and cause. Participants, caregivers, study coordinators, and investigators were masked to treatment assignment until data analysis was completed. The primary outcome was the proportion of children with exacerbation resolution by day 14 in the intention-to-treat population. Treatment groups were compared using generalised linear models. Statistical significance was set at p<0·0245 to account for multiple comparisons. This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12612000011886) and is completed.FindingsBetween April 17, 2012, and March 1, 2017, 604 children were screened and 252 were enrolled. Between July 31, 2012, and June 26, 2017, 197 children were allocated at the start of an exacerbation (63 to the amoxicillin–clavulanate group, 67 to the azithromycin group, and 67 to the placebo group). Respiratory viruses were identified in 82 (53%) of 154 children with available nasal swabs on day 1 of treatment. Primary outcome data were available for 196 (99%) children (one child with missing data [placebo group] was recorded as non-resolved according to criteria defined a priori). By day 14, exacerbations had resolved in 41 (65%) children in the amoxicillin–clavulanate group, 41 (61%) in the azithromycin group, and 29 (43%) in the placebo group. Compared with placebo, relative risk for resolution by day 14 was 1·50 (95% CI 1·08–2·09, p=0·015; number-needed-to-treat [NNT] 5 [95% CI 3–20]) in the amoxicillin–clavulanate group and 1·41 (1·01–1·97, p=0·042; NNT 6 [3–79]) in the azithromycin group. Adverse events were recorded in 19 (30%) children in the amoxicillin–clavulanate group, 20 (30%) in the azithromycin group, and 14 (21%) in the placebo group, but no events were severe or life-threatening.InterpretationAmoxicillin–clavulanate treatment is beneficial in terms of resolution of non-severe exacerbations of bronchiectasis in children, and should remain the first-line oral antibiotic in this setting.FundingNational Health and Medical Research Council (Australia), Cure Kids (New Zealand).

Health status deterioration in subjects with mild to moderate airflow obstruction, a six years observational study

BackgroundPatients with COPD need to cope with a disabling disease, which leads to health status impairment.AimTo investigate the long term change of health status in subjects with mild to moderate airflow obstruction and to compare this to subjects without airflow obstruction, with and without a smoking history. Second, to investigate the factors potentially associated to rapid health status decline in our total cohort.MethodsTwo hundred and one subjects were included. Generic [Short form 36 health survey (SF36) and EuroQol - 5 dimensions (EQ-5D)] and disease specific [Clinical COPD questionnaire (CCQ) and COPD Assessment Test (CAT)] health status questionnaires were regularly repeated over a six years period. Other functional outcomes comprised measures of lung function, physical fitness, physical activity and emotional state.ResultsOn average, health status decline did not differ between groups with the exception of the EQ-5D index, which deteriorated faster in subjects with airflow obstruction compared to the never smoking control group [− 0.018(0.008) versus 0.00006(0.003), p = 0.03]. Subjects presenting at least one exacerbation had faster rate of deterioration measured with CAT [0.91(0.21) versus − 0.26(0.25), p < 0.01]. Characteristics of the fast declining group were older age, worse lung function, physical fitness, physical activity and disease specific baseline health status. Subjects with airflow obstruction had a 2.5 (95% CI 1.36–4.71) higher risk of presenting fast overall health status decline. Fast overall decline was associated with the presence of acute exacerbation(s) (44% of the subjects with exacerbation(s) versus 17% of subjects without exacerbation, p = 0.03). Changes in fat free mass, functional exercise capacity and in symptoms of anxiety and depression correlated weakly to changes in health status measured with all questionnaires.ConclusionSubjects with mild airflow obstruction present a significant deterioration of health status, which is generally not much faster compared to smoking and never smoking controls. Subjects with fast decline in overall health status are older and more likely to have airflow obstruction, acute respiratory exacerbation(s), reduced physical fitness, physical activity and impaired COPD specific health status at baseline.Trial registrationNCT01314807 - retrospectively registered on March 2011.

Efficacy of Oral Antibiotics for Non-Severe Exacerbations of Bronchiectasis in Children (BEST 1): A Multi-Centre, Double-Blind, Double-Dummy, Randomised Placebo-Controlled Trial

Background: Bronchiectasis guidelines recommend antibiotics for treating acute respiratory exacerbations, but placebo-controlled, randomised-controlled trials (RCTs) are lacking in children. Since many exacerbations are virus-triggered, antibiotics may be unnecessary for non-severe (non-hospitalised) episodes. We hypothesised that oral amoxicillin-clavulanate and azithromycin are both superior to placebo for achieving symptom resolution by day-14 when treating non-severe exacerbations in children. Methods: In this multicentre (n=4), parallel, double-dummy, double-blind, placebo-controlled three-arm RCT, children aged 1-19 years were randomised at exacerbation onset to receive: (a) amoxicillin-clavulanate (45mg/kg/day)/azithromycin-placebo, (b) azithromycin (5mg/kg/day)/amoxicillin-clavulanate-placebo, or (c) placebo/placebo for 14-days (Australian-New Zealand Registry, ACTRN12612000011886). The primary outcome was exacerbation resolution by day-14. Secondary outcomes included exacerbation duration, time-to-next exacerbation, parent cough-specific quality-of-life, laboratory and spirometry assessments and nasopharyngeal microbiology. Treatment arms were compared using generalised-linear-models. Statistical significance was set at p<0·0245. Findings: Between April 2012 and December 2017, 197 children were randomised (amoxicillin-clavulanate n=63, azithromycin n=67, placebo n=67). By day-14, exacerbations had resolved in 41 (65%), 41 (61%) and 29 (43%) children in the respective groups. Compared to placebo, the relative risk of resolution by day-14 for amoxicillin-clavulanate was 1·50 (95% confidence interval [CI] 1·08-2·09; p=0·02, number needed-to-treat-for-benefit=5, 95%CI 3-20) and for azithromycin 1·41 (95%CI 1·01-1·97; p=0·04). Compared to placebo, the median exacerbation duration was significantly shorter in the amoxicillin-clavulanate (7 versus 10-days, p=0·02), but not the azithromycin group (8 vs 10-days, p=0·24). Other secondary between-group outcomes were not significantly different. Azithromycin was associated with increased nasopharyngeal carriage of macrolide-resistant-bacteria, while respiratory viruses were identified in 53% of exacerbations. Interpretation: Amoxicillin-clavulanate and azithromycin both showed benefit compared to placebo for treating non-severe exacerbations of bronchiectasis in children. However, azithromycin was associated with increased carriage of antibiotic-resistant bacteria. Consequently, amoxicillin-clavulanate should remain the first-line oral antibiotic for treating non-severe exacerbations of bronchiectasis in children. Funding: This work was supported by the Australian National Health and Medical Research Council (NHMRC; project grant number 1019834,) the NHMRC Centre for Research Excellence in Lung Health of Aboriginal and Torres Strait Islander Children (1040830), and Cure Kids, Auckland, New Zealand (3702764/3539). VG was supported by an NHMRC post-graduate scholarship (1075119). ABC is supported by an NHMRC practitioner fellowship (1058213). KFO and HSV were supported by NHMRC CRE in Children’s Indigenous Lung Health fellowships (10450830). MB is supported by a NHMRC Hot North Fellowship (1131932). Declaration of Interest: We declare that we have no conflicts of interest. Ethical Approval: The protocol has received ethical approval from the respective Human Research Ethics Committees of all the participating institutions (Darwin: Department of Health and Families and Menzies School of Health Research; Brisbane: Children’s Health Services (Royal Children’s Hospital) and University of Queensland; Perth: Princess Margaret Hospital; Melbourne: Royal Children’s Hospital; Auckland: Northern Ethics Committee, Ministry of Health and Starship Children’s Health local ethics committee). The study is being conducted under Australia’s Therapeutic Goods Administration Clinical Trial Notification scheme.

Vaccine Prophylaxis of Pneumococcal Infections in Children under Conditions of Severe Flood in the Amur River Basin.

Background Pneumococcal infection being one of the dominant causes of acute respiratory diseases and exacerbation of chronic ones is a serious problem for human health and society. The flood in the Amur river basin in the summer of 2013 created a special zone and risk conditions for the formation of respiratory pathology in the Far-Eastern region of Russia. We aimed to give clinical and epidemiological assessment of the effectiveness of vaccination programs of respiratory viral and pneumococcal infections and generalization of regional experience in the organization of a set of measures aimed at their prevention in the postflood period in the Far-Eastern region. Methods The monitoring program includes children aged 2 to 5 years in the amount of 4988 with risk factors for pneumococcal infection. The pneumococcal conjugate vaccine Prevenar-13 was used for immunization. Data on the incidence of ARVI and pneumonia in children in pre- and postvaccination periods were to be recorded. The indicators and special criteria were used to assess the effectiveness of vaccination. To study the circulation of serovariants of pneumococcus in inflammatory diseases of the respiratory tract and nasopharyngeal carrier, bacteriological and molecular genetic methods (RT-PCR in the mode of multiprime detection) were used. Results Differences in the frequency and range of serovariants of circulating isolates of pneumococcus in the postvaccinal period and in unvaccinated children, elimination of a number of serotypes, and appearance of circulation of nonvaccinated strains were revealed. The incidence of acute respiratory diseases and pneumonia among the vaccinated population for 2 years in the region decreased by 2.5 times. The coefficient of effectiveness of vaccination according to the indicator of morbidity of children with pneumonia reaches 75-100% with direct dependence on the age of children (r=0.98). Conclusion Comparative statistical analysis revealed a high degree of effectiveness of regional programs with the methods of immunoprophylaxis of pneumococcal infections.

Gene Expression Of TMEM178 Decreases With The Progression Of Asthma Severity

The transmembrane protein 178 (Tmem178) is a novel negative regulator of the nuclear factor of activated T-cells, cytoplasmic 1 (NFAT1c); a recognized player in asthma pathogenesis. Our group has previously shown that changes in TMEM178 gene expression are associated with lower airway obstruction in asthmatics having an acute respiratory illness-induced exacerbation. We sought to compare the relative gene expression of TMEM178 in the airway epithelium of severe asthmatics to that in the airway epithelium of non-severe asthmatics and healthy controls. We performed a secondary analysis of two high-quality publicly available microarray datasets (National Center for Biotechnology Information’s Gene Expression Omnibus database; accession numbers GSE43696 and GSE63142), which contained epithelial brushings obtained by bronchoscopy from asthmatics and healthy donors. For differential gene expression comparisons, moderated Benjamini-Hochberg t-tests (with false discovery rate adjustments) and Dunn’s multiple comparison tests were used. In the first microarray study (GSE43696), severe asthmatics had significantly lower levels of TMEM178 gene expression when compared to moderate asthmatics (p-value <0.05) and healthy controls (p-value <0.0001). Similarly, in the second microarray study (GSE63142), severe asthmatics had significantly lower levels of TMEM178 gene expression when compared to non-severe asthmatics (p-value <0.001) and healthy controls (p-value <0.0001). Overall, TMEM178 gene expression negatively correlates with asthma severity. In two independent microarray studies, the relative gene expression of TMEM178 decreased with the progression of asthma severity. We speculate that Tmem178 may play an important role in the regulation of NFAT-induced inflammation in severe asthmatics.

Effectiveness of Influenza Vaccination on Hospitalizations and Risk Factors for Severe Outcomes in Hospitalized Patients With COPD

The effectiveness of influenza vaccination in reducing influenza-related hospitalizations among patients with COPD is not well described, and influenza vaccination uptake remains suboptimal. Data were analyzed from a national, prospective, multicenter cohort study including patients with COPD, hospitalized with any acute respiratory illness or exacerbation between 2011 and 2015. All patients underwent nasopharyngeal swab screening with polymerase chain reaction (PCR) testing for influenza. The primary outcome was an influenza-related hospitalization. We identified influenza-positive cases and negative control subjects and used multivariable logistic regression with a standard test-negative design to estimate the vaccine effectiveness for preventing influenza-related hospitalizations. Among 4,755 hospitalized patients with COPD, 4,198 (88.3%) patients with known vaccination status were analyzed. The adjusted analysis showed a 38%reduction in influenza-related hospitalizations in vaccinated vsunvaccinated individuals. Influenza-positive patients (n= 1,833 [38.5%]) experienced higher crude mortality (9.7%vs7.9%; P= .047) and critical illness (17.2%vs12.1%; P< .001) compared with influenza-negative patients. Risk factors for mortality in influenza-positive patients included age > 75 years (OR, 3.7 [95%CI, 0.4-30.3]), cardiac comorbidity (OR, 2.0 [95%CI, 1.3-3.2]), residence in long-term care (OR, 2.6 [95%CI, 1.5-4.5]), and home oxygen use (OR, 2.9 [95%CI, 1.6-5.1]). Influenza vaccination significantly reduced influenza-related hospitalization among patients with COPD. Initiatives to increase vaccination uptake and early use of antiviral agents among patients with COPD could reduce influenza-related hospitalization and critical illness and improve health-care costs in this vulnerable population. ClinicalTrials.govNo.:NCT01517191; URL www.clinicaltrials.gov.

733. Incidence and Evaluation of the Change in Functional Status Associated with Respiratory Syncytial Virus Infection in Hospitalized Older Adults

BackgroundRespiratory Syncytial Virus (RSV) causes severe respiratory illnesses in infants and older adults. Mortality disproportionately affects the elderly, can exacerbate chronic cardiopulmonary conditions and may result in loss of function. The purpose of this study was to determine the incidence of RSV infection in hospitalized adults and evaluate functional changes associated with RSV hospitalization in older adults ≥60 years.MethodsAdults ≥18 years of age admitted with an acute respiratory infection (ARI) or exacerbation of chronic cardiopulmonary disease (e.g. CHF, COPD, asthma) preceded by an ARI within 14 days were screened. Subjects were included if hospitalized for ≥24 hours with laboratory confirmed RSV and residing in two catchment areas (Rochester, NY and New York, NY). Illness history, comorbidities and demographic characteristics were collected at enrollment. Enrolled subjects ≥60 years underwent functional status evaluation retrospectively 2 weeks prior to hospitalization, at enrollment, discharge and 2 months using the Lawton–Brody Instrumental Activity of Daily Living (IADL) Scale (0–8), Barthel (ADL) Index (0–100), MRC Breathlessness score (1–5) and Mini-Cog instrument.ResultsFrom October 2017 to March 2018, 2,883 adults hospitalized with ARI were tested and 322 (11%) positive for RSV. Seventy-two adults ≥60 years underwent functional assessment. Mean age was 75 years, 53% were female and 58% demonstrated impaired cognition on admission. Five subjects died during hospitalization and one prior to 2-month follow-up. Interim analysis of 2-month functional assessment was available for 39 subjects. RSV illness resulted in acute functional loss in almost all patients. Although there were no statistically significant differences between mean pre-hospitalization and 2-month functional scores, IADL (6.7 vs. 6.0, P = 0.27), ADL (90.4 vs. 88.5, P = 0.67) and MRC (2.96 vs. 2.7, P = 0.57), 23% of subjects required a higher level of care at discharge. Additionally, RSV hospitalization resulted in decreased ADL scores in 36% of subjects and worsening respiratory function in 18% assessed at 2 months (figure). ConclusionOlder adults hospitalized with RSV infection demonstrate acute functional decline which may result in prolonged loss of function in some patients.Disclosures A. Branche, Merck: Investigator, Grant recipient and Research grant. E. Granieri, Merck: Investigator, Research grant. E. Walsh, Merck: Investigator, Research grant. L. Finelli, Merck: Employee, Salary. A. R. Falsey, sanofi pasteur: Consultant and Grant Investigator, Consulting fee and Research grant. Gilead: Consultant, Consulting fee. Merck Sharpe and Dome: Investigator, Grant recipient. Janssen Pharmacueticals: Investigator, Grant recipient. Pfizer: Consultant, Research grant. Novavax: Consultant, none. A. Barrett, Merck: Investigator, Research support. L. Saiman, Merck: Investigator, Research grant.

Cough augmentation techniques for people with chronic neuromuscular disorders

Background People with neuromuscular disorders may have a weak, ineffective cough predisposing them to respiratory complications. Cough augmentation techniques aim to improve cough effectiveness and mucous clearance, reduce the frequency and duration of respiratory infections requiring hospital admission, and improve quality of life. Objectives To determine the efficacy and safety of cough augmentation techniques in adults and children with chronic neuromuscular disorders. Search methods On 13 April 2020, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and ClinicalTrials.gov for randomised controlled trials (RCTs), quasi-RCTs, and randomised cross-over trials. Selection criteria We included trials of cough augmentation techniques compared to no treatment, alternative techniques, or combinations thereof, in adults and children with chronic neuromuscular disorders. Data collection and analysis Two review authors independently assessed trial eligibility, extracted data, and assessed risk of bias. The primary outcomes were the number and duration of unscheduled hospitalisations for acute respiratory exacerbations. We assessed the certainty of evidence using GRADE. Main results The review included 11 studies involving 287 adults and children, aged three to 73 years. Inadequately reported cross-over studies and the limited additional information provided by authors severely restricted the number of analyses that could be performed. Studies compared manually assisted cough, mechanical insufflation, manual and mechanical breathstacking, mechanical insufflation-exsufflation, glossopharyngeal breathing, and combination techniques to unassisted cough and alternative or sham interventions. None of the included studies reported on the primary outcomes of this review (number and duration of unscheduled hospital admissions) or listed 'adverse events' as primary or secondary outcome measures. The evidence suggests that a range of cough augmentation techniques may increase peak cough flow compared to unassisted cough (199 participants, 8 RCTs), but the evidence is very uncertain. There may be little to no difference in peak cough flow outcomes between alternative cough augmentation techniques (216 participants, 9 RCTs). There was insufficient evidence to determine the effect of interventions on measures of gaseous exchange, pulmonary function, quality of life, general function, or participant preference and satisfaction. Authors' conclusions We are very uncertain about the safety and efficacy of cough augmentation techniques in adults and children with chronic neuromuscular disorders and further studies are needed.

Lung Function in Users of a Smoke-Free Electronic Device With HeatSticks (iQOS) Versus Smokers of Conventional Cigarettes: Protocol for a Longitudinal Cohort Observational Study.

BackgroundChronic obstructive pulmonary disease (COPD) is a global public health problem. It is the third-leading cause of death in the world, the fourth leading cause of death in Kazakhstan, and is strongly associated with smoking. Smoking cessation reduces the severity of respiratory symptoms and COPD exacerbations. Heated tobacco products, such as HeatSticks heated by the iQOS device, a smoke-free electronic device, may serve as less risky alternatives to conventional combustible cigarettes.ObjectiveThe purpose of this study is to evaluate frequency of exacerbations, respiratory symptoms, physical exercise intolerance, and abnormal lung functions, as well as other parameters and comorbidities among men and women aged 40-59 residing in Almaty, Kazakhstan, who use iQOS with HeatSticks compared to smokers of conventional cigarettes.MethodsThis is a 5-year single-center cohort observational study. It includes two cohorts of participants consisting of men and women aged 40-59 residing in the city of Almaty, Kazakhstan: (1) smokers of combustible cigarettes (control group) and (2) users of iQOS with HeatSticks (exposure group). The study has baseline and periodic (ie, annual) comprehensive clinical assessments, as well as continuous COPD case-finding activities and registration of acute respiratory exacerbations over the course of the 5-year observation period. Study measures include spirometry, chest computed tomography, electrocardiography, physical exams, laboratory testing of serum for biomarkers of inflammation and metabolic syndrome, anthropometry, and the 6-minute walk test. Information about COPD symptoms will be collected using the COPD Assessment Test.ResultsParticipant recruitment began December 2017, and enrollment is expected to last until late summer 2018.ConclusionsThis is the first cohort observational study in Kazakhstan to assess differences in lung function between users of the heated tobacco product, iQOS with HeatSticks, and smokers of conventional combustible cigarettes. The study results will add to knowledge on whether switching from combustible cigarettes to iQOS with HeatSticks affects respiratory symptoms and diseases, including the development and progression of COPD.Trial RegistrationClinicalTrials.gov NCT03383601; https://clinicaltrials.gov/ct2/show/NCT03383601 (Archived by WebCite at http://www.webcitation.org/72BYoAKxa)International Registered Report Identifier (IRRID)PRR1-10.2196/10006

Caseworker-assigned discharge plans to prevent hospital readmission for acute exacerbations in children with chronic respiratory illness.

Chronic respiratory conditions are major causes of mortality and morbidity. Children with chronic health conditions have increased morbidity associated with their physical, emotional, and general well-being. Acute respiratory exacerbations (AREs) are common in children with chronic respiratory disease, often requiring admission to hospital. Reducing the frequency of AREs and recurrent hospitalisations is therefore an important goal in the individual and public health management of chronic respiratory illnesses in children. Discharge planning is used to decide what a person needs for transition from one level of care to another and is usually considered in the context of discharge from hospital to the home. Discharge planning from hospital for ongoing management of an illness has historically been referral to a general practitioner or allied health professional or self management by the individual and their family with limited communication between the hospital and patient once discharged. Effective discharge planning can decrease the risk of recurrent AREs requiring medical care. An individual caseworker-assigned discharge plan may further decrease exacerbations. To evaluate the efficacy of individual caseworker-assigned discharge plans, as compared to non-caseworker-assigned plans, in preventing hospitalisation for AREs in children with chronic lung diseases such as asthma and bronchiectasis. We searched the Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, trials registries, and reference lists of articles. The latest searches were undertaken in November 2017. All randomised controlled trials comparing individual caseworker-assigned discharge planning compared to traditional discharge-planning approaches (including self management), and their effectiveness in reducing the subsequent need for emergency care for AREs (hospital admissions, emergency department visits, and/or unscheduled general practitioner visits) in children hospitalised with an acute exacerbation of chronic respiratory disease. We excluded studies that included children with cystic fibrosis. We used standard Cochrane Review methodological approaches. Relevant studies were independently selected in duplicate. Two review authors independently assessed trial quality and extracted data. We contacted the authors of one study for further information. We included four studies involving a total of 773 randomised participants aged between 14 months and 16 years. All four studies involved children with asthma, with the case-planning undertaken by a trained nurse educator. However, the discharge planning/education differed among the studies. We could include data from only two studies (361 children) in the meta-analysis. Two further studies enrolled children in both inpatient and outpatient settings, and one of these studies also included children with acute wheezing illness (no previous asthma diagnosis); the data specific to this review could not be obtained. For the primary outcome of exacerbations requiring hospitalisation, those in the intervention group were significantly less likely to be rehospitalised (odds ratio (OR) 0.29, 95% confidence interval (CI) 0.16 to 0.50) compared to controls. This equates to 189 (95% CI 124 to 236) fewer admissions per 1000 children. No adverse events were reported in any study. In the context of substantial statistical heterogeneity between the two studies, there were no statistically significant effects on emergency department (OR 0.37, 95% CI 0.04 to 3.05) or general practitioner (OR 0.87, 95% CI 0.22 to 3.44) presentations. There were no data on cost-effectiveness, length of stay of subsequent hospitalisations, or adherence to medications. One study reported quality of life, with no significant differences observed between the intervention and control groups.We considered three of the studies to have an unclear risk of bias, primarily due to inadequate description of the blinding of participants and investigators. The fourth study was assessed as at high risk of bias as a single unblinded investigator was used. Using the GRADE system, we assessed the quality of the evidence as moderate for the outcome of hospitalisation and low for the outcomes of emergency department visits and general practitioner consultations. Current evidence suggests that individual caseworker-assigned discharge plans, as compared to non-caseworker-assigned plans, may be beneficial in preventing hospital readmissions for acute exacerbations in children with asthma. There was no clear indication that the intervention reduces emergency department and general practitioner attendances for asthma, and there is an absence of data for children with other chronic respiratory conditions. Given the potential benefit and cost savings to the healthcare sector and families if hospitalisations and outpatient attendances can be reduced, there is a need for further randomised controlled trials encompassing different chronic respiratory illnesses, ethnicity, socio-economic settings, and cost-effectiveness, as well as defining the essential components of a complex intervention.

C‐reactive protein levels in acute respiratory exacerbations of cystic fibrosis

C-reactive protein (CRP) levels increase in response to bacterial infection and have been used to guide the use of antibiotics. We assessed CRP levels in a cohort of patients with cystic fibrosis (CF) admitted to hospital with an exacerbation of their lung disease, requiring treatment with broad-spectrum antibiotics. In this group, most subjects had CRP levels of less than 20 mg/L, including patients who had pneumonia. The clinical utility of the CRP in guiding antibiotic use in exacerbations of CF is limited.

Basophil counts in PBMC populations during childhood acute wheeze/asthma are associated with future exacerbations

Encapsulating summary Our data suggest that a basophil level above 0.18% of the PBMC population during an acute respiratory exacerbation is associated with an increased risk for future exacerbations in children with asthma and/or wheeze.

Daily use of extracorporeal CO2 removal in a critical care unit: indications and results

BackgroundWhile outcome improvement with extracorporeal CO2 removal (ECCO2R) is not demonstrated, a strong pathophysiological rational supports its use in the setting of acute respiratory distress syndrome (ARDS) and COPD exacerbation. We aimed to describe our single-center experience of ECCO2R indications and outcome.MethodsPatients treated with ECCO2R in our medial ICU, from March 2014 to November 2017, were retrospectively enrolled. Primary end point was evolution of ventilator settings during the two first days following ECCO2R start.ResultsThirty-three patients received ECCO2R. Seventeen were managed with Hemolung®, 10 with Prismalung®, 4 with ILA®, and 2 with Cardiohelp®. Indications for ECCO2R were mild or moderate ARDS (n = 16), COPD exacerbation (n = 11), or uncontrolled hypercapnia due to other causes (n = 6). Four patients were not intubated at the time of ECCO2R start. Median duration of ECCO2R treatment was 7 days [5–10]. In ARDS patients, between baseline and day 2, median tidal volume and driving pressure decreased from 5.3 [4.4–5.9] mL/kg and 10 [8–15] to 3.8 [3.3–4.1] mL/kg and 9 [8–11], respectively. Prone positioning was performed in 10 of the 16 patients, without serious adverse event. In COPD patients, between baseline and day 2, median ventilation minute and PaCO2 decreased significantly from respectively 7.6 [6.6–8.7] L/min and 9.4 [8.4–10.1] kPa to 5.8 [4.9–6.2] L/min and 6 [5.3–6.8] kPa. Four out of 11 COPD patients were extubated while on ECCO2R. Device thrombosis occurred in 5 patients (15%). Hemolysis was documented in 16 patients (48%). One patient died of intracranial hemorrhage, while on ECCO2R. Twenty-four patients were discharged from ICU alive. Twenty-eight day mortality was 31% in ARDS, 9% in COPD patients, and 50% in other causes of refractory hypercapnic respiratory failure.ConclusionECCO2R was useful to apply ultra-protective ventilation among ARDS patients and improved PaCO2, pH, and minute ventilation in COPD patients.

Inhaled corticosteroids for bronchiectasis.

Bronchiectasis is being increasingly diagnosed and recognised as an important contributor to chronic lung disease in both adults and children in high- and low-income countries. It is characterised by irreversible dilatation of airways and is generally associated with airway inflammation and chronic bacterial infection. Medical management largely aims to reduce morbidity by controlling the symptoms, reduce exacerbation frequency, improve quality of life and prevent the progression of bronchiectasis. This is an update of a review first published in 2000. To evaluate the efficacy and safety of inhaled corticosteroids (ICS) in children and adults with stable state bronchiectasis, specifically to assess whether the use of ICS: (1) reduces the severity and frequency of acute respiratory exacerbations; or (2) affects long-term pulmonary function decline. We searched the Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Register of trials, MEDLINE and Embase databases. We ran the latest literature search in June 2017. All randomised controlled trials (RCTs) comparing ICS with a placebo or no medication. We included children and adults with clinical or radiographic evidence of bronchiectasis, but excluded people with cystic fibrosis. We reviewed search results against predetermined criteria for inclusion. In this update, two independent review authors assessed methodological quality and risk of bias in trials using established criteria and extracted data using standard pro forma. We analysed treatment as 'treatment received' and performed sensitivity analyses. The review included seven studies, involving 380 adults. Of the 380 randomised participants, 348 completed the studies.Due to differences in outcomes reported among the seven studies, we could only perform limited meta-analysis for both the short-term ICS use (6 months or less) and the longer-term ICS use (> 6 months).During stable state in the short-term group (ICS for 6 months or less), based on the two studies from which data could be included, there were no significant differences from baseline values in the forced expiratory volume in the first second (FEV1) at the end of the study (mean difference (MD) -0.09, 95% confidence interval (CI) -0.26 to 0.09) and forced vital capacity (FVC) (MD 0.01 L, 95% CI -0.16 to 0.17) in adults on ICS (compared to no ICS). Similarly, we did not find any significant difference in the average exacerbation frequency (MD 0.09, 95% CI -0.61 to 0.79) or health-related quality of life (HRQoL) total scores in adults on ICS when compared with no ICS, though data available were limited. Based on a single non-placebo controlled study from which we could not extract clinical data, there was marginal, though statistically significant improvement in sputum volume and dyspnoea scores on ICS.The single study on long-term outcomes (over 6 months) that examined lung function and other clinical outcomes, showed no significant effect of ICS on any of the outcomes. We could not draw any conclusion on adverse effects due to limited available data.Despite the authors of all seven studies stating they were double-blind, we judged one study (in the short duration ICS) as having a high risk of bias based on blinding, attrition and reporting of outcomes. The GRADE quality of evidence was low for all outcomes (due to non-placebo controlled trial, indirectness and imprecision with small numbers of participants and studies). This updated review indicates that there is insufficient evidence to support the routine use of ICS in adults with stable state bronchiectasis. Further, we cannot draw any conclusion for the use of ICS in adults during an acute exacerbation or in children (for any state), as there were no studies.

Air pollution and emergency department visits for respiratory diseases: A multi-city case crossover study

Increasing evidence suggests that ambient air pollution is a major risk factor for both acute and chronic respiratory disease exacerbations and emergencies. The objective of this study was to determine the association between ambient air pollutants and emergency department (ED) visits for respiratory conditions in nine districts across the province of Ontario in Canada. Health, air pollutant (PM2.5, NO2, O3, and SO2), and meteorological data were retrieved from April 2004 to December 2011. Respiratory diseases were categorized as: chronic obstructive pulmonary disease (COPD, including bronchiectasis) and acute upper respiratory diseases. A case-crossover design was used to test the associations between ED visits and ambient air pollutants, stratified by sex and season. For COPD among males, positive results were observed for NO2 with lags of 3–6 days, for PM2.5 with lags 1–8, and for SO2 with lags of 4–8 days. For COPD among females, positive results were observed for O3 with lags 2–4 days, and for SO2 among lags of 3–6 days. For upper respiratory disease emergencies among males, positive results were observed for NO2 (lags 5–8 days), for O3, (lags 0–6 days), PM2.5 (all lags), and SO2 (lag 8), and among females, positive results were observed for NO2 for lag 8 days, for O3, PM2.5 among all lags. Our study provides evidence of the associations between short-term exposure to air pollution and increased risk of ED visits for upper and lower respiratory diseases in an environment where air pollutant concentrations are relatively low.

Epidemiology of S. Pneumoniae-associated Pneumonias and the Analysis of Effectiveness of Vaccination against Pneumococcal Infection in Children under the Age of Six

Pneumococcal infection is one of the main causes of acute respiratory diseases and exacerbation of chronic ones. In order to study the prevalence of community-acquired pneumonia, the etiologic role of S. pneumoniaе and effectiveness of vaccination among children under the age of 6 in the town of industrial cities, we conducted a non-interventional epidemiologic study of serotypes of circulating pneumococci and their compliance with the declared composition of vaccines recommended for prevention of pneumococcal infection in children. We also studied incidence rates of community-acquired pneumonias among children under the age of five vaccinated against pneumococcal infection, depending on the schedule and beginning of immunization. Our findings indicate a significant role of pneumococcus in the etiology of community-acquired pneumonias among children under the age of 17 (24.14%).The established spectrum of serotypes of pneumococcus from nasopharyngial swabs in children under the age of 17 with community-acquired pneumonia in the town of this city showed that such serotypes as 19F, 14, 9V/A, 15A/F, 6A/B/C, 3, and 23F contributed the most to the development of pneumonia (79.97%). Pneumococcus serotypes found corresponded to the composition of PCV13 in 76.36% of cases and to that of PCV10 – in 67.27%. Proven the effectiveness of the vaccine, the rate of epidemiologic effectiveness was 48.7% in relation to pneumonia of any etiology. Shown the largest epidemiological effectiveness (54.8%) of vaccination in children vaccinated in an early period (under the age of 1).