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Respirology (Carlton, Vic.) Mar 2020AATD is a common inherited disorder associated with an increased risk of developing pulmonary emphysema and liver disease. Many people with AATD-associated pulmonary... (Review)
Review
AATD is a common inherited disorder associated with an increased risk of developing pulmonary emphysema and liver disease. Many people with AATD-associated pulmonary emphysema remain undiagnosed and therefore without access to care and counselling specific to the disease. AAT augmentation therapy is available and consists of i.v. infusions of exogenous AAT protein harvested from pooled blood products. Its clinical efficacy has been the subject of some debate and the use of AAT augmentation therapy was recently permitted by regulators in Australia and New Zealand, although treatment is not presently subsidized by the government in either country. The purpose of this position statement is to review the evidence for diagnosis and treatment of AATD-related lung disease with reference to the Australian and New Zealand population. The clinical efficacy and adverse events of AAT augmentation therapy were evaluated by a systematic review, and the GRADE process was employed to move from evidence to recommendation. Other sections address the wide range of issues to be considered in the care of the individual with AATD-related lung disease: when and how to test for AATD, changing diagnostic techniques, monitoring of progression, disease in heterozygous AATD and pharmacological and non-pharmacological therapy including surgical options for severe disease. Consideration is also given to broader issues in AATD that respiratory healthcare staff may encounter: genetic counselling, patient support groups, monitoring for liver disease and the need to establish national registries for people with AATD in Australia and New Zealand.
Topics: Australia; Disease Progression; Humans; Lung Transplantation; New Zealand; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Plastic Surgery Procedures; alpha 1-Antitrypsin; alpha 1-Antitrypsin Deficiency
PubMed: 32030868
DOI: 10.1111/resp.13774 -
Medicine Jan 2020Bronchoscopic lung volume reduction (BLVR) offers alternative novel treatments for patients with emphysema. Comprehensive evidence for comparing different BLVR remains... (Meta-Analysis)
Meta-Analysis
Bronchoscopic lung volume reduction (BLVR) offers alternative novel treatments for patients with emphysema. Comprehensive evidence for comparing different BLVR remains unclear. To estimate the effects of different BLVR on patients with emphysema. PubMed, EMBASE, Cochrane Library, and Web of Science databases from January 2001 to August 2017 were searched. Randomized clinical trials evaluated effects of BLVR on patients with emphysema. The relevant information was extracted from the published reports with a predefined data extraction sheet, and the risk of bias was assessed with the Cochrane risk of bias tools. Pair-wise metaanalyses were made using the random-effects model. A random-effects network meta-analysis was applied within a Bayesian framework. The quality of evidence contributing to primary outcomes was assessed using the GRADE framework. 13 trials were deemed eligible, including 1993 participants. The quality of evidence was rated as moderate in most comparisons. Medical care (MC)was associated with the lowest adverse events compared with intrabronchial valve (IBV)(-2.5,[-4.70 to -0.29]), endobronchial valve (EBV) (-1.73, [-2.37 to -1.09]), lung volume reduction coils (LVRC) (-0.76, [-1.24 to -0.28]), emphysematous lung sealant (ELS) (-1.53, [-2.66 to -0.39]), and airway bypass(-1.57, [-3.74 to 0.61]). Adverse events in LVRC were lower compared with ELS (-0.77,[-2.00 to 0.47]). Bronchoscopic thermal vapor ablation (BTVA) showed significant improvement in FEV1 compared with MC (0.99, [0.37 to 1.62]), IBV (1.25, [0.25 to 2.25]), and LVRC (0.72, [0.03 to 1.40] ). Six minute walking distance (6 MWD) in ELS was significantly improved compared with other four BLVR, sham control, and MC (-1.96 to 1.99). Interestingly, MC showed less improvement in FEV1 and 6MWDcompared with EBV (-0.45, [-0.69 to -0.20] and -0.39, [-0.71 to -0.07], respectively). The mortality in MC and EBV was lower compared with LVRC alone (-0.38, [-1.16 to 0.41] and -0.50, [-1.68 to 0.68], respectively). BTVA and EBV led to significant changes in St George's respiratory questionnaire (SGRQ) compared with MC alone (-0.74, [-1.43 to -0.05] and 0.44, [0.11 to 0.78], respectively). BLVR offered a clear advantage for patients with emphysema. EBV had noticeable beneficial effects on the improvement of forced expiratory volume 1, 6MWD and SGRQ, and was associated with lower mortality compared with MC in different strategies of BLVR.
Topics: Bronchoscopy; Humans; Network Meta-Analysis; Pulmonary Emphysema
PubMed: 32000409
DOI: 10.1097/MD.0000000000018936 -
Chronic Respiratory Disease 2020Inhaled bronchodilators are the cornerstone of treatment for chronic obstructive pulmonary disease (COPD). Soft mist inhalers (SMIs) are devices that deliver... (Meta-Analysis)
Meta-Analysis
Inhaled bronchodilators are the cornerstone of treatment for chronic obstructive pulmonary disease (COPD). Soft mist inhalers (SMIs) are devices that deliver bronchodilators. Although correct device use is paramount to successful medication delivery, patient errors are common. This global systematic literature review and meta-analysis examined device use errors with SMIs among patients with obstructive lung diseases. PubMed, EMBASE, PsycINFO, Cochrane, and Google Scholar were searched to identify studies published between 2010 and 2019 that met the following inclusion criteria: (a) English language; (b) a diagnosis of COPD, bronchitis, or emphysema; and (c) reported device use errors among adults receiving long-acting bronchodilator treatment with Respimat® SMI (i.e. Spiriva®, Stiolto®, Spiolto®, and Striverdi®). Descriptive statistics examined sociodemographics, clinical characteristics, and device use errors. Meta-analysis techniques were employed with random-effects models to generate pooled mean effect sizes and 95% confidence intervals (CIs) for overall and step-by-step errors. The statistic measured heterogeneity. Twelve studies ( = 1288 patients) were included in this meta-analysis. Eighty-eight percent of patients had COPD, and most had moderate/very severe airflow limitation (Global Initiative for Chronic Obstructive Lung Disease spirometric stages II to IV). Aggregate results revealed that 58.9% (95% CI: 42.4-75.5; = 92.8%) of patients made ≥1 device use errors. Among 11 studies with step-by-step data, the most common errors were failure to (1) exhale completely and away from the device (47.8% (95% CI: 33.6-62.0)); (2) hold breath for up to 10 seconds (30.6% (95% CI: 17.5-43.7)); (3) take a slow, deep breath while pressing the dose release button (27.9% (95% CI: 14.5-41.2)); (4) hold the inhaler upright (22.6% (95% CI: 6.2-39.0)); and (5) turn the base toward the arrows until it clicked (17.6% (95% CI: 3.0-32.2)). Device use errors occurred in about 6 of 10 patients who used SMIs. An individualized approach to inhalation device selection and ongoing training and monitoring of device use are important in optimizing bronchodilator treatment.
Topics: Administration, Inhalation; Albuterol, Ipratropium Drug Combination; Bronchodilator Agents; Humans; Metered Dose Inhalers; Pulmonary Disease, Chronic Obstructive; Self Administration
PubMed: 31984767
DOI: 10.1177/1479973119901234 -
Therapeutic Advances in Respiratory... 2019Combined pulmonary fibrosis and emphysema (CPFE) is a syndrome characterized by the coexistence of upper lobe emphysema and lower lobe fibrosis. However, whether CPFE... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Combined pulmonary fibrosis and emphysema (CPFE) is a syndrome characterized by the coexistence of upper lobe emphysema and lower lobe fibrosis. However, whether CPFE has a higher or lower mortality than idiopathic pulmonary fibrosis (IPF) alone is still not clear. In this study we conducted a meta-analysis to assess the survival rate (SR) of CPFE IPF alone in clinical trials.
METHODS
We performed a systematic search of PubMed, Embase, and the Cochrane Central Register of Controlled Trials for trials published prior to 31 March 2018. Extracts from the literature were analyzed with Review Manager version 5.3.
RESULTS
Thirteen eligible trials were included in this analysis (involving 1710 participants). Overall, the pooled results revealed that no statistically significant difference was detected in the 1-year [relative risk (RR) = 0.98, 95% confidence interval (CI): 0.94-1.03, = 0.47], 3-year (RR = 0.83, 95% CI: 0.68-1.01, = 0.06), and 5-year (RR = 0.80, 95% CI: 0.59-1.07, = 0.14) SRs of CPFE IPF alone.
CONCLUSIONS
CPFE exhibits a very poor prognosis, similar to IPF alone. Additional studies are needed to provide more convincing data to investigate the natural history and outcome of patients with CPFE in comparison to IPF.
Topics: Humans; Idiopathic Pulmonary Fibrosis; Prognosis; Pulmonary Emphysema; Survival Rate
PubMed: 31722622
DOI: 10.1177/1753466619888119 -
The Cochrane Database of Systematic... May 2019Chronic obstructive pulmonary disease (COPD; including chronic bronchitis and emphysema) is a chronic respiratory condition characterised by shortness of breath, cough...
BACKGROUND
Chronic obstructive pulmonary disease (COPD; including chronic bronchitis and emphysema) is a chronic respiratory condition characterised by shortness of breath, cough and recurrent exacerbations. Long-term antibiotic use may reduce both bacterial load and inflammation in the airways. Studies have shown a reduction of exacerbations with antibiotics in comparison to placebo in people with COPD, but there are concerns about antibiotic resistance and safety.
OBJECTIVES
To compare the safety and efficacy of different classes of antibiotics (continuous, intermittent or pulsed) for prophylaxis of exacerbations in patients with COPD.
SEARCH METHODS
We searched the Cochrane Airways Group Trials Register and bibliographies of relevant studies. The latest literature search was conducted on 6 February 2019.
SELECTION CRITERIA
Randomised controlled trials (RCTs) were selected that compared one prophylactic antibiotic with another in patients with COPD.
DATA COLLECTION AND ANALYSIS
We used the standard Cochrane methods. Two independent review authors selected trials for inclusion, extracted data and assessed risk of bias. Discrepancies were resolved by involving a third review author.
MAIN RESULTS
We included two RCTs, both published in 2015 involving a total of 391 participants with treatment duration of 12 to 13 weeks. One RCT compared a quinolone (moxifloxacin pulsed, for 5 days every 4 weeks), with a tetracycline (doxycycline continuous) or a macrolide (azithromycin intermittent).The second RCT compared a tetracycline (doxycycline continuous) plus a macrolide (roxithromycin continuous), with roxithromycin (continuous) alone.The trials recruited participants with a mean age of 68 years, with moderate-severity COPD. Both trials included participants who had between two and five exacerbations in the previous one to two years. In one trial, 17% of patients had previously been using inhaled corticosteroids. In the other study, all patients were positive for Chlamydophila pneumoniae (C pneumoniae).Overall, we judged the evidence presented to be of very low-certainty, mainly due to imprecision, but we also had concerns about indirectness and methodological quality of the included studies. The primary outcome measures for this review included exacerbations, quality of life, drug resistance and serious adverse events.Macrolide + tetracycline versus macrolide There was no clear difference between treatments in improvement in quality of life as assessed by the Chronic Respiratory Questionnaire (CRQ). The CRQ scale ranges from 0 to 10 and higher scores on the scale indicate better quality of life. CRQ sub-scales for dyspnoea (mean difference (MD) 0.58, 95% confidence interval (CI) -0.84 to 2.00; 187 participants; very low-certainty evidence), fatigue (MD 0.02, 95% CI -1.08 to 1.12; 187 participants; very low-certainty evidence), emotional function (MD -0.37, 95% CI -1.74 to 1.00; 187 participants; very low-certainty evidence), or mastery (MD -0.79, 95% CI -1.86 to 0.28; 187 participants; very low-certainty evidence) at 12 weeks. For serious adverse events, it was uncertain if there was a difference between combined roxithromycin and doxycycline versus roxithromycin alone at 48 weeks follow-up after active treatment of 12 weeks (odds ratio (OR) 1.00, 95% CI 0.52 to 1.93; 198 participants; very low-certainty evidence). There were five deaths reported in the combined treatment arm, versus three in the single treatment arm at 48 weeks follow-up after active treatment of 12 weeks (OR 1.63, 95% CI 0.38 to 7.02; 198 participants; very low-certainty evidence).Quinolone versus tetracycline There was no clear difference between moxifloxacin and doxycycline for the number of participants experiencing one or more exacerbations (OR 0.44, 95% CI 0.14 to 1.38; 50 participants, very low-certainty evidence) at 13 weeks. There were no serious adverse events or deaths reported in either treatment groups. We did not identify any evidence for our other primary outcomes.Quinolone versus macrolide There was no clear difference between moxifloxacin and azithromycin for the number of participants experiencing one or more exacerbations (OR 1.00, 95% CI 0.32 to 3.10; 50 participants; very low-certainty evidence) at 13 weeks. There were no serious adverse events or deaths reported in either treatment groups. We did not identify any evidence for our other primary outcomes.Marcolide versus tetracycline There was no clear difference between azithromycin and doxycycline for the number of participants experiencing one or more exacerbations (OR 0.44, 95% CI 0.14 to 1.38; 50 participants; very low-certainty evidence) at 13 weeks. There were no serious adverse events or deaths reported in either treatment groups. We did not identify any evidence for our other primary outcomes.We did not find head-to-head evidence for impact of antibiotics on drug resistance.
AUTHORS' CONCLUSIONS
It is not clear from the evidence included in this review whether there is a difference in efficacy or safety between different classes or regimens of prophylactic antibiotic, given for 12 to 13 weeks to people with COPD. Whilst no head-to-head comparisons of antibiotic resistance were identified, concerns about this continue. The sample size in this review is small and both included studies are of short duration. Thus, there is considerable uncertainty in effects observed and the effects of different prophylactic antibiotics requires further research.
Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Disease Progression; Humans; Pulmonary Disease, Chronic Obstructive; Quality of Life; Treatment Outcome
PubMed: 31125127
DOI: 10.1002/14651858.CD013024.pub2 -
BMJ Open Feb 2019To identify, characterise and explain common and specific features of the experience of treatment burden in relation to patients living with lung cancer or chronic...
Patients and informal caregivers' experiences of burden of treatment in lung cancer and chronic obstructive pulmonary disease (COPD): a systematic review and synthesis of qualitative research.
OBJECTIVE
To identify, characterise and explain common and specific features of the experience of treatment burden in relation to patients living with lung cancer or chronic obstructive pulmonary disease (COPD) and their informal caregivers.
DESIGN
Systematic review and interpretative synthesis of primary qualitative studies. Papers were analysed using constant comparison and directed qualitative content analysis.
DATA SOURCES
CINAHL, EMBASE, MEDLINE, PsychINFO, Scopus and Web of Science searched from January 2006 to December 2015.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Primary qualitative studies in English where participants were patients with lung cancer or COPD and/or their informal caregivers, aged >18 years that contain descriptions of experiences of interacting with health or social care in Europe, North America and Australia.
RESULTS
We identified 127 articles with 1769 patients and 491 informal caregivers. Patients, informal caregivers and healthcare professionals (HCPs) acknowledged lung cancer's existential threat. Managing treatment workload was a priority in this condition, characterised by a short illness trajectory. Treatment workload was generally well supported by an immediacy of access to healthcare systems and a clear treatment pathway. Conversely, patients, informal caregivers and HCPs typically did not recognise or understand COPD. Treatment workload was balanced with the demands of everyday life throughout a characteristically long illness trajectory. Consequently, treatment workload was complicated by difficulties of access to, and navigation of, healthcare systems, and a fragmented treatment pathway. In both conditions, patients' capacity to manage workload was enhanced by the support of family and friends, peers and HCPs and diminished by illness/smoking-related stigma and social isolation.
CONCLUSION
This interpretative synthesis has affirmed significant differences in treatment workload between lung cancer and COPD. It has demonstrated the importance of the capacity patients have to manage their workload in both conditions. This suggests a workload which exceeds capacity may be a primary driver of treatment burden.
PROSPERO REGISTRATION NUMBER
CRD42016048191.
Topics: Caregivers; Cost of Illness; Humans; Lung Neoplasms; Pulmonary Disease, Chronic Obstructive; Qualitative Research
PubMed: 30813114
DOI: 10.1136/bmjopen-2017-020515 -
American Journal of Industrial Medicine May 2019Non-malignant respiratory disease (NMRD) cases have occurred among rubber manufacturing workers. We examined exposure to rubber manufacturing emissions as a risk factor... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Non-malignant respiratory disease (NMRD) cases have occurred among rubber manufacturing workers. We examined exposure to rubber manufacturing emissions as a risk factor for NMRD.
METHODS
From a systematic literature review, we identified case reports and assessed cross-sectional and mortality studies for strength of evidence of positive association (strong, intermediate, non-significant positive association, none) between exposure to rubber manufacturing emissions and NMRD-related morbidity and mortality, and conducted two meta-analyses.
RESULTS
We analyzed 62 articles. We identified 11 cases of NMRD. Nine (30%) of 30 cross-sectional studies and one (4%) of 26 mortality studies had strong evidence. The summary odds ratio and SMR for the cross-sectional and mortality meta-analyses were 3.83 (95% confidence interval [CI], 2.28-6.51) and 0.90 (95%CI, 0.82-0.99), respectively.
CONCLUSION
Available evidence supports rubber manufacturing emissions as a potential risk factor for NMRD-related morbidity. Further investigations with longer follow-up periods and inclusion of short-tenured workers could further define risks for NMRD and identify prevention strategies.
Topics: Humans; Manufacturing Industry; Occupational Diseases; Occupational Exposure; Respiration Disorders; Rubber
PubMed: 30775791
DOI: 10.1002/ajim.22959 -
Current Pediatric Reviews 2019Alpha1-antitrypsin (AAT) deficiency is a common, but an underdiagnosed genetic condition, affecting 1 in 1500 individuals. It can present insidiously with liver disease...
IMPORTANCE
Alpha1-antitrypsin (AAT) deficiency is a common, but an underdiagnosed genetic condition, affecting 1 in 1500 individuals. It can present insidiously with liver disease in children. Although clinical practice guidelines exist for the management of AAT deficiency, especially with regards to pulmonary involvement, there are no published recommendations that specifically relate to the management of the liver disease and monitoring for lung disease associated with this condition, particularly in children.
OBJECTIVE
To review the literature on the management of AAT deficiency-associated liver disease in adults and children.
EVIDENCE REVIEW
A systematic search for articles indexed in PubMed and published was undertaken. Some earlier selected landmark references were included in the review. Search terms included: "alpha1-antitrypsin deficiency"; "liver disease"; "end-stage liver disease"; "liver transplantation" and "preventative management". Recommendations for the management of children with suspected or confirmed AAT deficiency were made according to the Strength of Recommendation Taxonomy scale.
FINDINGS
Liver complications arising from AAT deficiency result from the accumulation of mutated AAT protein within hepatocytes. Liver disease occurs in 10% of children, manifested by cholestasis, pruritus, poor feeding, hepatomegaly, and splenomegaly, but the presentation is highly variable. A diagnostic test for AAT deficiency is recommended for these children. Baseline liver function tests should be obtained to assess for liver involvement; however, the only curative treatment for AAT deficiency-associated liver disease is organ transplantation. Conclusion and Relevance: There should be a greater vigilance for AAT deficiency testing among pediatricians. Diagnosis should prompt assessment of liver involvement. Children with AATdeficiency- associated liver disease should be referred to a liver specialist and monitored throughout their lifetimes for the symptoms of AAT-deficiency-related pulmonary involvement.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Infant; Liver; Liver Diseases; Liver Transplantation; Male; Transition to Adult Care; alpha 1-Antitrypsin Deficiency
PubMed: 30421678
DOI: 10.2174/1573396314666181113094517 -
International Journal of Chronic... 2018The aim of the study was to assess the relationship between computed tomography (CT) densitometry and routine clinical markers in patients with chronic obstructive... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The aim of the study was to assess the relationship between computed tomography (CT) densitometry and routine clinical markers in patients with chronic obstructive pulmonary disease (COPD) and alpha-1 anti-trypsin deficiency (AATD).
METHODS
Multiple databases were searched using a combination of pertinent terms and those articles relating quantitatively measured CT densitometry to clinical outcomes. Studies that used visual scoring only were excluded, as were those measured in expiration only. A thorough review of abstracts and full manuscripts was conducted by 2 reviewers; data extraction and assessment of bias was conducted by 1 reviewer and the 4 reviewers independently assessed for quality. Pooled correlation coefficients were calculated, and heterogeneity was explored.
RESULTS
A total of 112 studies were identified, 82 being suitable for meta-analysis. The most commonly used density threshold was -950 HU, and a significant association between CT density and all included clinical parameters was demonstrated. There was marked heterogeneity between studies secondary to large variety of disease severity within commonly included cohorts and differences in CT acquisition parameters.
CONCLUSION
CT density shows a good relationship to clinically relevant parameters; however, study heterogeneity and lack of longitudinal data mean that it is difficult to compare studies or derive a minimal clinically important difference. We recommend that international consensus is reached to standardize CT conduct and analysis in future COPD and AATD studies.
Topics: Aged; Chi-Square Distribution; Densitometry; Female; Forced Expiratory Volume; Humans; Lung; Male; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Pulmonary Diffusing Capacity; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Quality of Life; Severity of Illness Index; Spirometry; Tomography, X-Ray Computed; Vital Capacity; alpha 1-Antitrypsin Deficiency
PubMed: 29445272
DOI: 10.2147/COPD.S143066 -
BMJ Open Respiratory Research 2018Chronic obstructive pulmonary disease (COPD) is a major and growing cause of morbidity and mortality worldwide. The global prevalence of COPD is growing faster in women...
INTRODUCTION
Chronic obstructive pulmonary disease (COPD) is a major and growing cause of morbidity and mortality worldwide. The global prevalence of COPD is growing faster in women than in men. Women are often exposed to indoor pollutants produced by biomass fuels burning during household activities.
METHODS
We conducted a meta-analysis to establish the association between COPD and exposure to biomass smoke in women.Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched MEDLINE and Scopus databases in 31December 2016, with the terms: "wood", "charcoal", "biomass", "solid fuels", "organic fuel", "biofuel", "female", "women", "COPD", "chronic bronchitis", "emphysema", "chronic obstructive pulmonary disease". Studies were eligible if they were case-control or cross-sectional studies involving exposure to indoor biomass smoke, conducted at any time and in any geographic location. Fixed-effects or random-effects meta-analysis was used to generate pooled OR.
RESULTS
24 studies were included: 5 case-control studies and 19 cross-sectional studies. Biomass-exposed individuals were 1.38 times more likely to be diagnosed with COPD than non-exposed (OR 1.38, 95% CI 1.28 to 1.57).Spirometry-diagnosed COPD studies failed to show a significant association (OR 1.20, 95% CI 0.99 to 1.40). Nevertheless, the summary estimate of OR for chronic bronchitis (CB) was significant (OR 2.11, 95% CI 1.70 to 2.52). The pooled OR for cross-sectional studies and case-control studies were respectively 1.82 (95% CI 1.54 to 2.10) and 1.05 (95% CI 0.81 to 1.30). Significant association was found between COPD and biomass smoke exposure for women living as well in rural as in urban areas.
CONCLUSIONS
This study showed that biomass smoke exposure is associated with COPD in rural and urban women.In many developing countries, modern fuels are more and more used alongside traditional ones, mainly in urban area. Data are needed to further explore the benefit of the use of mixed fuels for cooking on respiratory health, particularly on COPD reduction.
PubMed: 29387422
DOI: 10.1136/bmjresp-2017-000246