#COPD and #asthma: the emergency is clear, now is the time for action
http://www.thelancet.com/journals/lanres/article/PIIS2213-2600(17)30308-9/fulltext
An excellent Article1 has been published in The Lancet Respiratory Medicine on the risk and disease estimates of chronic obstructive pulmonary disease (COPD) and asthma as part of the Global Burden of Disease Study (GBD) 2015. The Article provides a good overview of the mortality, prevalence, disability-adjusted life years (DALYs), and years lived with disability for the two most common respiratory diseases. The findings show that the prevalence of and mortality due to COPD, as well as the prevalence of asthma, increased between 1990 and 2015. However, age-standardised results indicate that this phenomenon is mainly due to an ageing population. Globally, more than 174 million people have COPD and more than 358 million people have asthma. With an ageing population, this number is expected to increase, especially for COPD. Mortality due to COPD is eight times higher than mortality due to asthma. COPD and—to a lesser extent—asthma clearly impose a substantial burden in terms of both impaired quality of life and physical, psychological, and social disability
http://www.thelancet.com/journals/lanres/article/PIIS2213-2600(17)30308-9/fulltext
An excellent Article1 has been published in The Lancet Respiratory Medicine on the risk and disease estimates of chronic obstructive pulmonary disease (COPD) and asthma as part of the Global Burden of Disease Study (GBD) 2015. The Article provides a good overview of the mortality, prevalence, disability-adjusted life years (DALYs), and years lived with disability for the two most common respiratory diseases. The findings show that the prevalence of and mortality due to COPD, as well as the prevalence of asthma, increased between 1990 and 2015. However, age-standardised results indicate that this phenomenon is mainly due to an ageing population. Globally, more than 174 million people have COPD and more than 358 million people have asthma. With an ageing population, this number is expected to increase, especially for COPD. Mortality due to COPD is eight times higher than mortality due to asthma. COPD and—to a lesser extent—asthma clearly impose a substantial burden in terms of both impaired quality of life and physical, psychological, and social disability
#Tezepelumab in Adults with Uncontrolled #Asthma
http://www.nejm.org/doi/full/10.1056/NEJMoa1704064
In some patients with moderate-to-severe asthma, particularly those with noneosinophilic inflammation, the disease remains uncontrolled. This trial evaluated the efficacy and safety of tezepelumab (AMG 157/MEDI9929), a human monoclonal antibody specific for the epithelial-cell–derived cytokine thymic stromal lymphopoietin (TSLP), in patients whose asthma remained uncontrolled despite treatment with long-acting beta-agonists and medium-to-high doses of inhaled glucocorticoids
The use of tezepelumab at a dose of 70 mg every 4 weeks (low dose; 145 patients), 210 mg every 4 weeks (medium dose; 145 patients), or 280 mg every 2 weeks (high dose; 146 patients) resulted in annualized asthma exacerbation rates at week 52 of 0.26, 0.19, and 0.22, respectively, as compared with 0.67 in the placebo group (148 patients). Thus, exacerbation rates in the respective tezepelumab groups were lower by 61%, 71%, and 66% than the rate in the placebo group (P<0.001 for all comparisons). Similar results were observed in patients regardless of blood eosinophil counts at enrollment. The prebronchodilator forced expiratory volume in 1 second at week 52 was higher in all tezepelumab groups than in the placebo group (difference, 0.12 liters with the low dose P=0.01, 0.11 liters with the medium dose P=0.02, and 0.15 liters with the high dose P=0.002). A total of 2 patients in the medium-dose group, 3 in the high-dose group, and 1 in the placebo group discontinued the trial regimen because of adverse events.
Conclusions
Among patients treated with long-acting beta-agonists and medium-to-high doses of inhaled glucocorticoids, those who received tezepelumab had lower rates of clinically significant asthma exacerbations than those who received placebo, independent of baseline blood eosinophil counts
http://www.nejm.org/doi/full/10.1056/NEJMoa1704064
In some patients with moderate-to-severe asthma, particularly those with noneosinophilic inflammation, the disease remains uncontrolled. This trial evaluated the efficacy and safety of tezepelumab (AMG 157/MEDI9929), a human monoclonal antibody specific for the epithelial-cell–derived cytokine thymic stromal lymphopoietin (TSLP), in patients whose asthma remained uncontrolled despite treatment with long-acting beta-agonists and medium-to-high doses of inhaled glucocorticoids
The use of tezepelumab at a dose of 70 mg every 4 weeks (low dose; 145 patients), 210 mg every 4 weeks (medium dose; 145 patients), or 280 mg every 2 weeks (high dose; 146 patients) resulted in annualized asthma exacerbation rates at week 52 of 0.26, 0.19, and 0.22, respectively, as compared with 0.67 in the placebo group (148 patients). Thus, exacerbation rates in the respective tezepelumab groups were lower by 61%, 71%, and 66% than the rate in the placebo group (P<0.001 for all comparisons). Similar results were observed in patients regardless of blood eosinophil counts at enrollment. The prebronchodilator forced expiratory volume in 1 second at week 52 was higher in all tezepelumab groups than in the placebo group (difference, 0.12 liters with the low dose P=0.01, 0.11 liters with the medium dose P=0.02, and 0.15 liters with the high dose P=0.002). A total of 2 patients in the medium-dose group, 3 in the high-dose group, and 1 in the placebo group discontinued the trial regimen because of adverse events.
Conclusions
Among patients treated with long-acting beta-agonists and medium-to-high doses of inhaled glucocorticoids, those who received tezepelumab had lower rates of clinically significant asthma exacerbations than those who received placebo, independent of baseline blood eosinophil counts
New England Journal of Medicine
Tezepelumab in Adults with Uncontrolled Asthma | NEJM
Original Article from The New England Journal of Medicine — Tezepelumab in Adults with Uncontrolled Asthma
Long-Acting Beta agonists (LABAs) and Inhaled Corticosteroids (ICS): Drug Safety Communication - Boxed #Warning About #Asthma-Related Death Removed
https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm590001.htm
FDA's most prominent warning, the Boxed Warning, about asthma-related death has been removed from the drug labels of medicines that contain both an ICS and LABA. A FDA review of four large clinical safety trials shows that treating asthma with long-acting beta agonists (LABAs) in combination with inhaled corticosteroids (ICS) does not result in significantly more serious asthma-related side effects than treatment with ICS alone. A description of the four trials is now also included in the Warnings and Precautions section of the drug labels. These trials showed that LABAs, when used with ICS, did not significantly increase the risk of asthma-related hospitalizations, the need to insert a breathing tube known as intubation, or asthma-related deaths, compared to ICS alone.
https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm590001.htm
FDA's most prominent warning, the Boxed Warning, about asthma-related death has been removed from the drug labels of medicines that contain both an ICS and LABA. A FDA review of four large clinical safety trials shows that treating asthma with long-acting beta agonists (LABAs) in combination with inhaled corticosteroids (ICS) does not result in significantly more serious asthma-related side effects than treatment with ICS alone. A description of the four trials is now also included in the Warnings and Precautions section of the drug labels. These trials showed that LABAs, when used with ICS, did not significantly increase the risk of asthma-related hospitalizations, the need to insert a breathing tube known as intubation, or asthma-related deaths, compared to ICS alone.
www.fda.gov
Long-Acting Beta agonists (LABAs) and Inhaled Corticosteroids (ICS): Drug Safety Communication - Boxed Warning About Asthma-Related…
FDA review of clinical safety trials shows that treating asthma with LABAs in combination with ICS does not result in significantly more serious asthma-related side effects than treatment with ICS alone.
Association of Inhaled Corticosteroids and Long-Acting #Muscarinic Antagonists With Asthma Control in Patients With Uncontrolled, Persistent #Asthma
https://jamanetwork.com/journals/jama/fullarticle/2675736
Of 1326 records identified, 15 randomized clinical trials (N = 7122 patients) were included. Most trials assessed adding LAMA vs placebo or LAMA vs LABA to inhaled corticosteroids. Adding LAMA vs placebo to inhaled corticosteroids was associated with a significantly reduced risk of exacerbation requiring systemic corticosteroids (RR, 0.67 95% CI, 0.48 to 0.92; RD, −0.02 95% CI, −0.04 to 0.00). Compared with adding LABA, adding LAMA to inhaled corticosteroids was not associated with significant improvements in exacerbation risk (RR, 0.87 95% CI, 0.53 to 1.42; RD, 0.00 95% CI, −0.02 to 0.02), or any other outcomes of interest. Triple therapy was not significantly associated with improved exacerbation risk vs inhaled corticosteroids and LABA (RR, 0.84 95% CI, 0.57 to 1.22; RD, −0.01 95% CI, −0.08 to 0.07).
Conclusions and Relevance In this systematic review and meta-analysis, the use of LAMA compared with placebo as add-on therapy to inhaled corticosteroids was associated with a lower risk of asthma exacerbations; however, the association of LAMA with benefit may not be greater than that with LABA. Triple therapy was not associated with a lower risk of exacerbations
https://jamanetwork.com/journals/jama/fullarticle/2675736
Of 1326 records identified, 15 randomized clinical trials (N = 7122 patients) were included. Most trials assessed adding LAMA vs placebo or LAMA vs LABA to inhaled corticosteroids. Adding LAMA vs placebo to inhaled corticosteroids was associated with a significantly reduced risk of exacerbation requiring systemic corticosteroids (RR, 0.67 95% CI, 0.48 to 0.92; RD, −0.02 95% CI, −0.04 to 0.00). Compared with adding LABA, adding LAMA to inhaled corticosteroids was not associated with significant improvements in exacerbation risk (RR, 0.87 95% CI, 0.53 to 1.42; RD, 0.00 95% CI, −0.02 to 0.02), or any other outcomes of interest. Triple therapy was not significantly associated with improved exacerbation risk vs inhaled corticosteroids and LABA (RR, 0.84 95% CI, 0.57 to 1.22; RD, −0.01 95% CI, −0.08 to 0.07).
Conclusions and Relevance In this systematic review and meta-analysis, the use of LAMA compared with placebo as add-on therapy to inhaled corticosteroids was associated with a lower risk of asthma exacerbations; however, the association of LAMA with benefit may not be greater than that with LABA. Triple therapy was not associated with a lower risk of exacerbations
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As-Needed Budesonide–Formoterol versus Maintenance #Budesonide in Mild #Asthma
https://www.nejm.org/doi/full/10.1056/NEJMoa1715275
.. Budesonide–formoterol used as needed was noninferior to budesonide maintenance therapy for severe exacerbations; the annualized rate of severe exacerbations was 0.11 (95% confidence interval CI, 0.10 to 0.13) and 0.12 (95% CI, 0.10 to 0.14), respectively (rate ratio, 0.97; upper one-sided 95% confidence limit, 1.16). The median daily metered dose of inhaled glucocorticoid was lower in the budesonide–formoterol group (66 μg) than in the budesonide maintenance group (267 μg). The time to the first exacerbation was similar in the two groups (hazard ratio, 0.96; 95% CI, 0.78 to 1.17). The change in ACQ-5 score showed a difference of 0.11 units (95% CI, 0.07 to 0.15) in favor of budesonide maintenance therapy.
CONCLUSIONS
In patients with mild asthma, budesonide–formoterol used as needed was noninferior to twice-daily budesonide with respect to the rate of severe asthma exacerbations during 52 weeks of treatment but was inferior in controlling symptoms. Patients in the budesonide–formoterol group had approximately one quarter of the inhaled glucocorticoid exposure of those in the budesonide maintenance group
As-Needed Budesonide–Formoterol versus Maintenance #Budesonide in Mild #Asthma
https://www.nejm.org/doi/full/10.1056/NEJMoa1715275
.. Budesonide–formoterol used as needed was noninferior to budesonide maintenance therapy for severe exacerbations; the annualized rate of severe exacerbations was 0.11 (95% confidence interval CI, 0.10 to 0.13) and 0.12 (95% CI, 0.10 to 0.14), respectively (rate ratio, 0.97; upper one-sided 95% confidence limit, 1.16). The median daily metered dose of inhaled glucocorticoid was lower in the budesonide–formoterol group (66 μg) than in the budesonide maintenance group (267 μg). The time to the first exacerbation was similar in the two groups (hazard ratio, 0.96; 95% CI, 0.78 to 1.17). The change in ACQ-5 score showed a difference of 0.11 units (95% CI, 0.07 to 0.15) in favor of budesonide maintenance therapy.
CONCLUSIONS
In patients with mild asthma, budesonide–formoterol used as needed was noninferior to twice-daily budesonide with respect to the rate of severe asthma exacerbations during 52 weeks of treatment but was inferior in controlling symptoms. Patients in the budesonide–formoterol group had approximately one quarter of the inhaled glucocorticoid exposure of those in the budesonide maintenance group
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Association of Inhaled Corticosteroids and Long-Acting β-Agonists as Controller and Quick Relief Therapy With #Exacerbations and Symptom Control in Persistent #Asthma
https://jamanetwork.com/journals/jama/article-abstract/2675737
The analyses included 16 randomized clinical trials (N = 22 748 patients), 15 of which evaluated SMART as a combination therapy with budesonide and formoterol in a dry-powder inhaler. Among patients aged 12 years or older (n = 22 524; mean age, 42 years; 14 634 65% were female), SMART was associated with a reduced risk of asthma exacerbations compared with the same dose of inhaled corticosteroids and LABA as the controller therapy (RR, 0.68 95% CI, 0.58 to 0.80; RD, −6.4% 95% CI, −10.2% to −2.6%) and a higher dose of inhaled corticosteroids and LABA as the controller therapy (RR, 0.77 95% CI, 0.60 to 0.98; RD, −2.8% 95% CI, −5.2% to −0.3%). Similar results were seen when SMART was compared with inhaled corticosteroids alone as the controller therapy. Among patients aged 4 to 11 years (n = 341; median age, 8 range, 4-11 years; 69 31% were female), SMART was associated with a reduced risk of asthma exacerbations compared with a higher dose of inhaled corticosteroids as the controller therapy (RR, 0.55 95% CI, 0.32 to 0.94; RD, −12.0% 95% CI, −22.5% to −1.5%) or the same dose of inhaled corticosteroids and LABA as the controller therapy (RR, 0.38 95% CI, 0.23 to 0.63; RD, −23.2% 95% CI, −33.6% to −12.1%).
Conclusions and Relevance In this meta-analysis of patients with persistent asthma, the use of single maintenance and reliever therapy compared with inhaled corticosteroids as the controller therapy (with or without a long-acting β-agonist) and short-acting β-agonists as the relief therapy was associated with a lower risk of asthma exacerbations. Evidence for patients aged 4 to 11 years was limited
Association of Inhaled Corticosteroids and Long-Acting β-Agonists as Controller and Quick Relief Therapy With #Exacerbations and Symptom Control in Persistent #Asthma
https://jamanetwork.com/journals/jama/article-abstract/2675737
The analyses included 16 randomized clinical trials (N = 22 748 patients), 15 of which evaluated SMART as a combination therapy with budesonide and formoterol in a dry-powder inhaler. Among patients aged 12 years or older (n = 22 524; mean age, 42 years; 14 634 65% were female), SMART was associated with a reduced risk of asthma exacerbations compared with the same dose of inhaled corticosteroids and LABA as the controller therapy (RR, 0.68 95% CI, 0.58 to 0.80; RD, −6.4% 95% CI, −10.2% to −2.6%) and a higher dose of inhaled corticosteroids and LABA as the controller therapy (RR, 0.77 95% CI, 0.60 to 0.98; RD, −2.8% 95% CI, −5.2% to −0.3%). Similar results were seen when SMART was compared with inhaled corticosteroids alone as the controller therapy. Among patients aged 4 to 11 years (n = 341; median age, 8 range, 4-11 years; 69 31% were female), SMART was associated with a reduced risk of asthma exacerbations compared with a higher dose of inhaled corticosteroids as the controller therapy (RR, 0.55 95% CI, 0.32 to 0.94; RD, −12.0% 95% CI, −22.5% to −1.5%) or the same dose of inhaled corticosteroids and LABA as the controller therapy (RR, 0.38 95% CI, 0.23 to 0.63; RD, −23.2% 95% CI, −33.6% to −12.1%).
Conclusions and Relevance In this meta-analysis of patients with persistent asthma, the use of single maintenance and reliever therapy compared with inhaled corticosteroids as the controller therapy (with or without a long-acting β-agonist) and short-acting β-agonists as the relief therapy was associated with a lower risk of asthma exacerbations. Evidence for patients aged 4 to 11 years was limited
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#Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled #Asthma
https://www.nejm.org/doi/full/10.1056/NEJMoa1804092?query=featured_home
At week 12, the FEV1 had increased by 0.32 liters in patients assigned to the lower dose of dupilumab (difference vs. matched placebo, 0.14 liters; P<0.001); similar results were seen with the higher dose. Among patients with a blood eosinophil count of 300 or more per cubic millimeter, the annualized rate of severe asthma exacerbations was 0.37 (95% CI, 0.29 to 0.48) among those receiving lower-dose dupilumab and 1.08 (95% CI, 0.85 to 1.38) among those receiving a matched placebo (65.8% lower rate with dupilumab than with placebo; 95% CI, 52.0 to 75.6); similar results were observed with the higher dose. Blood eosinophilia occurred after the start of the intervention in 52 patients (4.1%) who received dupilumab as compared with 4 patients (0.6%) who received placebo.
CONCLUSIONS
In this trial, patients who received dupilumab had significantly lower rates of severe asthma exacerbation than those who received placebo, as well as better lung function and asthma control. Greater benefits were seen in patients with higher baseline levels of eosinophils. Hypereosinophilia was observed in some patients.
#Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled #Asthma
https://www.nejm.org/doi/full/10.1056/NEJMoa1804092?query=featured_home
At week 12, the FEV1 had increased by 0.32 liters in patients assigned to the lower dose of dupilumab (difference vs. matched placebo, 0.14 liters; P<0.001); similar results were seen with the higher dose. Among patients with a blood eosinophil count of 300 or more per cubic millimeter, the annualized rate of severe asthma exacerbations was 0.37 (95% CI, 0.29 to 0.48) among those receiving lower-dose dupilumab and 1.08 (95% CI, 0.85 to 1.38) among those receiving a matched placebo (65.8% lower rate with dupilumab than with placebo; 95% CI, 52.0 to 75.6); similar results were observed with the higher dose. Blood eosinophilia occurred after the start of the intervention in 52 patients (4.1%) who received dupilumab as compared with 4 patients (0.6%) who received placebo.
CONCLUSIONS
In this trial, patients who received dupilumab had significantly lower rates of severe asthma exacerbation than those who received placebo, as well as better lung function and asthma control. Greater benefits were seen in patients with higher baseline levels of eosinophils. Hypereosinophilia was observed in some patients.
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Combined Analysis of #Asthma Safety Trials of Long-Acting #β2-Agonists
https://www.nejm.org/doi/full/10.1056/NEJMoa1716868
Among the 36,010 patients in the intention-to-treat study, there were three asthma-related intubations (two in the inhaled-glucocorticoid group and one in the combination-therapy group) and two asthma-related deaths (both in the combination-therapy group) in 4 patients. In the secondary analysis of serious asthma-related events (a composite of hospitalization, intubation, or death), 108 of 18,006 patients (0.60%) in the inhaled-glucocorticoid group and 119 of 18,004 patients (0.66%) in the combination-therapy group had at least one composite event (relative risk in the combination-therapy group, 1.09; 95% confidence interval CI, 0.83 to 1.43; P=0.55); 2100 patients in the inhaled-glucocorticoid group (11.7%) and 1768 in the combination-therapy group (9.8%) had at least one asthma exacerbation (relative risk, 0.83; 95% CI, 0.78 to 0.89; P<0.001).
CONCLUSIONS
Combination therapy with a LABA plus an inhaled glucocorticoid did not result in a significantly higher risk of serious asthma-related events than treatment with an inhaled glucocorticoid alone but resulted in significantly fewer asthma exacerbations
Combined Analysis of #Asthma Safety Trials of Long-Acting #β2-Agonists
https://www.nejm.org/doi/full/10.1056/NEJMoa1716868
Among the 36,010 patients in the intention-to-treat study, there were three asthma-related intubations (two in the inhaled-glucocorticoid group and one in the combination-therapy group) and two asthma-related deaths (both in the combination-therapy group) in 4 patients. In the secondary analysis of serious asthma-related events (a composite of hospitalization, intubation, or death), 108 of 18,006 patients (0.60%) in the inhaled-glucocorticoid group and 119 of 18,004 patients (0.66%) in the combination-therapy group had at least one composite event (relative risk in the combination-therapy group, 1.09; 95% confidence interval CI, 0.83 to 1.43; P=0.55); 2100 patients in the inhaled-glucocorticoid group (11.7%) and 1768 in the combination-therapy group (9.8%) had at least one asthma exacerbation (relative risk, 0.83; 95% CI, 0.78 to 0.89; P<0.001).
CONCLUSIONS
Combination therapy with a LABA plus an inhaled glucocorticoid did not result in a significantly higher risk of serious asthma-related events than treatment with an inhaled glucocorticoid alone but resulted in significantly fewer asthma exacerbations
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#Lipid profiles in adolescents with and without #asthma: Korea National Health and nutrition examination survey data
https://lipidworld.biomedcentral.com/articles/10.1186/s12944-018-0807-4
There were 123 adolescents with asthma and 2718 without asthma (controls). The TC/HDL-C ratio, LDL-C/HDL-C ratio, and non-HDL-C levels were significantly higher in the asthma group than in the non-asthma group (P < 0.05). The high-risk groups displayed significantly higher asthma prevalence with higher TC, TG, LDL-C, and non-HDL-C levels and TG/HDL-C ratio than the low-risk groups (P < 0.05). After adjusting for potential confounding factors, the high-risk groups were associated with asthma according to their higher TC levels (adjusted odds ratio, 1.69; 95% confidence interval, 1.012–2.822) and TG/HDL-C ratios (adjusted odds ratio, 1.665; 95% confidence interval, 1.006–2.756).
Conclusions
Asthma prevalence was greater in adolescents with a high TC level and TG/HDL-C ratio. In addition to the standard lipid profile, elevated TG/HDL-C ratio can be used as a useful additional lipid measure to evaluate interactions between dyslipidemia and asthma
#Lipid profiles in adolescents with and without #asthma: Korea National Health and nutrition examination survey data
https://lipidworld.biomedcentral.com/articles/10.1186/s12944-018-0807-4
There were 123 adolescents with asthma and 2718 without asthma (controls). The TC/HDL-C ratio, LDL-C/HDL-C ratio, and non-HDL-C levels were significantly higher in the asthma group than in the non-asthma group (P < 0.05). The high-risk groups displayed significantly higher asthma prevalence with higher TC, TG, LDL-C, and non-HDL-C levels and TG/HDL-C ratio than the low-risk groups (P < 0.05). After adjusting for potential confounding factors, the high-risk groups were associated with asthma according to their higher TC levels (adjusted odds ratio, 1.69; 95% confidence interval, 1.012–2.822) and TG/HDL-C ratios (adjusted odds ratio, 1.665; 95% confidence interval, 1.006–2.756).
Conclusions
Asthma prevalence was greater in adolescents with a high TC level and TG/HDL-C ratio. In addition to the standard lipid profile, elevated TG/HDL-C ratio can be used as a useful additional lipid measure to evaluate interactions between dyslipidemia and asthma
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Association of #Antibiotic Treatment With Outcomes in Patients Hospitalized for an #Asthma Exacerbation Treated With Systemic Corticosteroids
https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2721036
Although professional society guidelines discourage use of empirical antibiotics in the treatment of asthma exacerbation, high antibiotic prescribing rates have been recorded in the United States and elsewhere
Compared with patients not treated with antibiotics, treated patients were older (median [IQR] age, 48 [36-61] vs 45 [32-57] years), more likely to be white (48.6% vs 40.9%) and smokers (6.6% vs 5.3%), and had a higher number of comorbidities (eg, congestive heart failure, 6.2% vs 5.8%). Those treated with antibiotics had a significantly longer hospital stay (median [IQR], 4 [3-5] vs 3 [2-4] days) and a similar rate of treatment failure (5.4% vs 5.8%). In propensity score–matched analysis, receipt of antibiotics was associated with a 29% longer hospital stay (length of stay ratio, 1.29; 95% CI, 1.27-1.31) and higher cost of hospitalization (median [IQR] cost, $4776 [$3219-$7373] vs $3641 [$2346-$5942]) but with no difference in the risk of treatment failure (propensity score–matched OR, 0.95; 95% CI, 0.82-1.11). Multivariable adjustment, propensity score weighting, and instrumental variable analysis as well as several sensitivity analyses yielded similar results.
Conclusions and Relevance Antibiotic therapy may be associated with a longer hospital length of stay, higher hospital cost, and similar risk of treatment failure. These results highlight the need to reduce inappropriate antibiotic prescribing among patients hospitalized for asthma
Association of #Antibiotic Treatment With Outcomes in Patients Hospitalized for an #Asthma Exacerbation Treated With Systemic Corticosteroids
https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2721036
Although professional society guidelines discourage use of empirical antibiotics in the treatment of asthma exacerbation, high antibiotic prescribing rates have been recorded in the United States and elsewhere
Compared with patients not treated with antibiotics, treated patients were older (median [IQR] age, 48 [36-61] vs 45 [32-57] years), more likely to be white (48.6% vs 40.9%) and smokers (6.6% vs 5.3%), and had a higher number of comorbidities (eg, congestive heart failure, 6.2% vs 5.8%). Those treated with antibiotics had a significantly longer hospital stay (median [IQR], 4 [3-5] vs 3 [2-4] days) and a similar rate of treatment failure (5.4% vs 5.8%). In propensity score–matched analysis, receipt of antibiotics was associated with a 29% longer hospital stay (length of stay ratio, 1.29; 95% CI, 1.27-1.31) and higher cost of hospitalization (median [IQR] cost, $4776 [$3219-$7373] vs $3641 [$2346-$5942]) but with no difference in the risk of treatment failure (propensity score–matched OR, 0.95; 95% CI, 0.82-1.11). Multivariable adjustment, propensity score weighting, and instrumental variable analysis as well as several sensitivity analyses yielded similar results.
Conclusions and Relevance Antibiotic therapy may be associated with a longer hospital length of stay, higher hospital cost, and similar risk of treatment failure. These results highlight the need to reduce inappropriate antibiotic prescribing among patients hospitalized for asthma
Jamanetwork
Antibiotic Treatment and Outcomes in Patients Hospitalized for an Asthma Exacerbation
This cohort study uses data from the Premier Inpatient Database to assess outcomes associated with the addition of antibiotic treatment in patients hospitalized for asthma exacerbation treated with corticosteroids who had no other indication for antibiotic…
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Vitamin #D Status Modifies the Response to Indoor Particulate Matter in Obese Urban Children with #Asthma
https://www.sciencedirect.com/science/article/pii/S2213219819301606?via%3Dihub
Children were of mean (standard deviation [SD]) age 9.7 (2.2) years, 36% were obese, and 95% self-reported black race. Mean (SD) PM2.5 indoor exposure was 38.2 (42.9) μg/m3 and 25-OH D was 19.1 (7.5) ng/mL. Three-way interaction models demonstrated significantly greater PM2.5-associated effects on daytime asthma symptoms only among obese children with low 25-OH D levels (odds ratio [OR]PM2.5 = 1.26, P = .049 at vitamin D = 15.5 ng/mL, increasingly stronger PM effects at levels <15.5 ng/mL). In homes with increased PM2.5, higher 25-OH D was associated with decreased symptom odds (eg, ORVitamin D = 0.87; P = .049 at PM2.5 = 52.5 μg/m3, increasingly protective effects >52.5 μg/m3) among obese children.
Conclusions
Among obese urban children with asthma, low individual 25-OH D enhanced adverse respiratory effects associated with indoor PM2.5. In high PM2.5 environments, 25-OH D was protective against asthma symptoms. Optimizing vitamin D status in children may help reduce asthma morbidity driven by indoor air pollution.
Vitamin #D Status Modifies the Response to Indoor Particulate Matter in Obese Urban Children with #Asthma
https://www.sciencedirect.com/science/article/pii/S2213219819301606?via%3Dihub
Children were of mean (standard deviation [SD]) age 9.7 (2.2) years, 36% were obese, and 95% self-reported black race. Mean (SD) PM2.5 indoor exposure was 38.2 (42.9) μg/m3 and 25-OH D was 19.1 (7.5) ng/mL. Three-way interaction models demonstrated significantly greater PM2.5-associated effects on daytime asthma symptoms only among obese children with low 25-OH D levels (odds ratio [OR]PM2.5 = 1.26, P = .049 at vitamin D = 15.5 ng/mL, increasingly stronger PM effects at levels <15.5 ng/mL). In homes with increased PM2.5, higher 25-OH D was associated with decreased symptom odds (eg, ORVitamin D = 0.87; P = .049 at PM2.5 = 52.5 μg/m3, increasingly protective effects >52.5 μg/m3) among obese children.
Conclusions
Among obese urban children with asthma, low individual 25-OH D enhanced adverse respiratory effects associated with indoor PM2.5. In high PM2.5 environments, 25-OH D was protective against asthma symptoms. Optimizing vitamin D status in children may help reduce asthma morbidity driven by indoor air pollution.
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Association Between Pre-Diabetes/ #Diabetes and Asthma Exacerbations in a Claims-Based Obese #Asthma Cohort
https://www.jaci-inpractice.org/article/S2213-2198(19)30244-2/abstract
Metabolic dysfunction may contribute to worsened asthma in obesity. The relationship between pre-diabetes and diabetes, metabolic conditions more common in obesity, and asthma outcomes is not well-characterized.
Individuals with a hemoglobin A1c (HbA1c) measurement were identified, categorized as within normal (<5.6%), pre-diabetes (5.7-6.4%), and diabetes (≥6.5%) ranges. Exacerbations, defined as asthma-related hospitalization, emergency department visit, or corticosteroid prescription ±14 days of an asthma-related outpatient visit, were ascertained
5,722 individuals were identified. Higher HgbA1c was associated with higher asthma exacerbation rates. In the fully-adjusted model, compared to individuals with normal HbA1c, those in the pre-diabetes range had a 27% higher rate (95% CI, 5%-52%), and those in the diabetes range had a 33% higher rate (95% CI, 2%-73%).
Conclusion
Pre-diabetes and diabetes were associated with higher rates of asthma exacerbation among obese adults with asthma. Results support evidence that insulin resistance and metabolic syndrome, metabolic features common in pre-diabetes/diabetes, can influence asthma morbidity.
Association Between Pre-Diabetes/ #Diabetes and Asthma Exacerbations in a Claims-Based Obese #Asthma Cohort
https://www.jaci-inpractice.org/article/S2213-2198(19)30244-2/abstract
Metabolic dysfunction may contribute to worsened asthma in obesity. The relationship between pre-diabetes and diabetes, metabolic conditions more common in obesity, and asthma outcomes is not well-characterized.
Individuals with a hemoglobin A1c (HbA1c) measurement were identified, categorized as within normal (<5.6%), pre-diabetes (5.7-6.4%), and diabetes (≥6.5%) ranges. Exacerbations, defined as asthma-related hospitalization, emergency department visit, or corticosteroid prescription ±14 days of an asthma-related outpatient visit, were ascertained
5,722 individuals were identified. Higher HgbA1c was associated with higher asthma exacerbation rates. In the fully-adjusted model, compared to individuals with normal HbA1c, those in the pre-diabetes range had a 27% higher rate (95% CI, 5%-52%), and those in the diabetes range had a 33% higher rate (95% CI, 2%-73%).
Conclusion
Pre-diabetes and diabetes were associated with higher rates of asthma exacerbation among obese adults with asthma. Results support evidence that insulin resistance and metabolic syndrome, metabolic features common in pre-diabetes/diabetes, can influence asthma morbidity.
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Controlled Trial of #Budesonide– #Formoterol as Needed for Mild #Asthma
https://www.nejm.org/doi/full/10.1056/NEJMoa1901963
In double-blind, placebo-controlled trials, budesonide–formoterol used on an as-needed basis resulted in a lower risk of severe exacerbation of asthma than as-needed use of a short-acting β2-agonist (SABA); the risk was similar to that of budesonide maintenance therapy plus as-needed SABA..
..The number of severe exacerbations was lower in the budesonide–formoterol group than in both the albuterol group (9 vs. 23; relative risk, 0.40; 95% CI, 0.18 to 0.86) and the budesonide maintenance group (9 vs. 21; relative risk, 0.44; 95% CI, 0.20 to 0.96). The mean (±SD) dose of inhaled budesonide was 107±109 μg per day in the budesonide–formoterol group and 222±113 μg per day in the budesonide maintenance group. The incidence and type of adverse events reported were consistent with those in previous trials and with reports in clinical use.
CONCLUSIONS
In an open-label trial involving adults with mild asthma, budesonide–formoterol used as needed was superior to albuterol used as needed for the prevention of asthma exacerbations.
Controlled Trial of #Budesonide– #Formoterol as Needed for Mild #Asthma
https://www.nejm.org/doi/full/10.1056/NEJMoa1901963
In double-blind, placebo-controlled trials, budesonide–formoterol used on an as-needed basis resulted in a lower risk of severe exacerbation of asthma than as-needed use of a short-acting β2-agonist (SABA); the risk was similar to that of budesonide maintenance therapy plus as-needed SABA..
..The number of severe exacerbations was lower in the budesonide–formoterol group than in both the albuterol group (9 vs. 23; relative risk, 0.40; 95% CI, 0.18 to 0.86) and the budesonide maintenance group (9 vs. 21; relative risk, 0.44; 95% CI, 0.20 to 0.96). The mean (±SD) dose of inhaled budesonide was 107±109 μg per day in the budesonide–formoterol group and 222±113 μg per day in the budesonide maintenance group. The incidence and type of adverse events reported were consistent with those in previous trials and with reports in clinical use.
CONCLUSIONS
In an open-label trial involving adults with mild asthma, budesonide–formoterol used as needed was superior to albuterol used as needed for the prevention of asthma exacerbations.
New England Journal of Medicine
Controlled Trial of Budesonide–Formoterol as Needed for Mild Asthma | NEJM
Original Article from The New England Journal of Medicine — Controlled Trial of Budesonide–Formoterol as Needed for Mild Asthma
Single #inhaler extrafine triple therapy in uncontrolled #asthma (TRIMARAN and TRIGGER): two double-blind, parallel-group, randomised, controlled phase 3 trials
..extrafine combination of beclometasone dipropionate (BDP; inhaled corticosteroid), formoterol fumarate (FF; long-acting β 2 agonist), and glycopyrronium (G; long-acting muscarinic antagonist) with the combination of BDP with FF
..Compared with the BDP/FF group, week 26 predose FEV 1 improved in the BDP/FF/G group by 57 mL (95% CI 15–99; p=0·0080) in TRIMARAN and by 73 mL (26–120; p=0·0025) in TRIGGER, with reductions in the rate of moderate and severe exacerbations of 15% (rate ratio 0·85, 95% CI 0·73–0·99; p=0·033) in TRIMARAN and 12% (0·88, 0·75–1·03; p=0·11) in TRIGGER. Four patients had treatment-related serious adverse events, one in TRIMARAN in the BDP/FF/G group and three in TRIGGER—one in the BDP/FF/G and two in the BDP/FF group. Three patients in the BDP/FF/G group in TRIMARAN and two patients in TRIGGER—one in the BDP/FF/G group and one in the BDP/FF group—had adverse events leading to death. None of the deaths were considered as related to treatment.
Interpretation
In uncontrolled asthma, addition of a long-acting muscarinic antagonist to inhaled corticosteroid plus long-acting β 2-agonist therapy improves lung function and reduces exacerbations
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)32215-9/fulltext
..extrafine combination of beclometasone dipropionate (BDP; inhaled corticosteroid), formoterol fumarate (FF; long-acting β 2 agonist), and glycopyrronium (G; long-acting muscarinic antagonist) with the combination of BDP with FF
..Compared with the BDP/FF group, week 26 predose FEV 1 improved in the BDP/FF/G group by 57 mL (95% CI 15–99; p=0·0080) in TRIMARAN and by 73 mL (26–120; p=0·0025) in TRIGGER, with reductions in the rate of moderate and severe exacerbations of 15% (rate ratio 0·85, 95% CI 0·73–0·99; p=0·033) in TRIMARAN and 12% (0·88, 0·75–1·03; p=0·11) in TRIGGER. Four patients had treatment-related serious adverse events, one in TRIMARAN in the BDP/FF/G group and three in TRIGGER—one in the BDP/FF/G and two in the BDP/FF group. Three patients in the BDP/FF/G group in TRIMARAN and two patients in TRIGGER—one in the BDP/FF/G group and one in the BDP/FF group—had adverse events leading to death. None of the deaths were considered as related to treatment.
Interpretation
In uncontrolled asthma, addition of a long-acting muscarinic antagonist to inhaled corticosteroid plus long-acting β 2-agonist therapy improves lung function and reduces exacerbations
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)32215-9/fulltext
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Sex Steroid #Hormones and #Asthma in a Nationwide Study of U.S. Adults
Women have a higher burden of asthma than men. Although sex hormones may explain sex differences in asthma, their role is unclear..
..Free testosterone levels in the fourth quartile were associated with lower odds of current asthma in women (odds ratio [OR] for the fourth quartile [Q4] vs. Q1, 0.56; 95% confidence interval [CI], 0.39–0.80). Given an interaction between obesity and sex hormones on current asthma, we stratified the analysis by obesity. In this analysis, elevated free testosterone (OR for Q4 vs. Q1, 0.59; 95% CI, 0.37–0.91) and estradiol (OR for Q4 vs. Q1, 0.43; 95% CI, 0.23–0.78) levels were associated with reduced odds of current asthma in obese women, and an elevated serum estradiol was associated with lower odds of current asthma in nonobese men (OR for Q4 vs. Q1, 0.44; 95% CI, 0.21–0.90).
Conclusions: Our findings suggest that sex hormones play a role in known sex differences in asthma in adults. Moreover, our results suggest that obesity modifies the effects of sex hormones on asthma in adults.
https://bit.ly/38mpK1d
Sex Steroid #Hormones and #Asthma in a Nationwide Study of U.S. Adults
Women have a higher burden of asthma than men. Although sex hormones may explain sex differences in asthma, their role is unclear..
..Free testosterone levels in the fourth quartile were associated with lower odds of current asthma in women (odds ratio [OR] for the fourth quartile [Q4] vs. Q1, 0.56; 95% confidence interval [CI], 0.39–0.80). Given an interaction between obesity and sex hormones on current asthma, we stratified the analysis by obesity. In this analysis, elevated free testosterone (OR for Q4 vs. Q1, 0.59; 95% CI, 0.37–0.91) and estradiol (OR for Q4 vs. Q1, 0.43; 95% CI, 0.23–0.78) levels were associated with reduced odds of current asthma in obese women, and an elevated serum estradiol was associated with lower odds of current asthma in nonobese men (OR for Q4 vs. Q1, 0.44; 95% CI, 0.21–0.90).
Conclusions: Our findings suggest that sex hormones play a role in known sex differences in asthma in adults. Moreover, our results suggest that obesity modifies the effects of sex hormones on asthma in adults.
https://bit.ly/38mpK1d
www.atsjournals.org
Sex Steroid Hormones and Asthma in a Nationwide Study of U.S. Adults | American Journal of Respiratory and Critical Care Medicine
Rationale: Women have a higher burden of asthma than men. Although sex hormones may explain sex differences in asthma, their role is unclear.Objectives: To examine sex hormone levels and asthma in ...
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Persistent #Asthma is Associated with Increased Risk for Incident Atrial #Fibrillation in the Multi-Ethnic Study of Atherosclerosis (MESA)
Asthma and atrial fibrillation (AF) share an underlying inflammatory pathophysiology. We hypothesized that persistent asthmatics are at higher risk for developing AF and that this association would be attenuated by adjustment for baseline markers of systemic inflammation.
..Persistent asthma was defined as asthma requiring use of controller medications. Intermittent asthma was defined as asthma without use of controller medications..
..In risk-factor adjusted models, persistent asthmatics had a greater risk of incident AF (hazard ratio [HR] 1.49 [95% CI 1.03-2.14], p=0.03). Interleukin 6 (IL-6, HR 1.26 [95% CI 1.13-1.42]), tumor necrosis factor-α receptor 1 (TNF-α R1, HR 1.09 [95% CI 1.08-1.11]) and D-Dimer (HR 1.10 [95% CI 1.02-1.20]) predicted incident AF, but the relationship between asthma and incident AF was not attenuated by adjustment for any inflammation marker (IL-6, C-reactive protein, TNF-α R1, D-dimer, fibrinogen).
Conclusions - In a large multiethnic cohort with nearly 13 years follow-up, persistent asthma was associated with increased risk for incident AF. This association was not attenuated by adjustment for baseline inflammatory biomarkers
https://bit.ly/37jbG7L
Persistent #Asthma is Associated with Increased Risk for Incident Atrial #Fibrillation in the Multi-Ethnic Study of Atherosclerosis (MESA)
Asthma and atrial fibrillation (AF) share an underlying inflammatory pathophysiology. We hypothesized that persistent asthmatics are at higher risk for developing AF and that this association would be attenuated by adjustment for baseline markers of systemic inflammation.
..Persistent asthma was defined as asthma requiring use of controller medications. Intermittent asthma was defined as asthma without use of controller medications..
..In risk-factor adjusted models, persistent asthmatics had a greater risk of incident AF (hazard ratio [HR] 1.49 [95% CI 1.03-2.14], p=0.03). Interleukin 6 (IL-6, HR 1.26 [95% CI 1.13-1.42]), tumor necrosis factor-α receptor 1 (TNF-α R1, HR 1.09 [95% CI 1.08-1.11]) and D-Dimer (HR 1.10 [95% CI 1.02-1.20]) predicted incident AF, but the relationship between asthma and incident AF was not attenuated by adjustment for any inflammation marker (IL-6, C-reactive protein, TNF-α R1, D-dimer, fibrinogen).
Conclusions - In a large multiethnic cohort with nearly 13 years follow-up, persistent asthma was associated with increased risk for incident AF. This association was not attenuated by adjustment for baseline inflammatory biomarkers
https://bit.ly/37jbG7L
www.ahajournals.org
Persistent Asthma is Associated with Increased Risk for Incident Atrial Fibrillation in the Multi-Ethnic Study of Atherosclerosis…
Background - Asthma and atrial fibrillation (AF) share an underlying inflammatory pathophysiology. We hypothesized that persistent asthmatics are at higher risk for developing AF and that this asso...
Sputum #microbiome profiles identify severe #asthma phenotypes of relative stability at 12-18 months
https://2medical.news/2020/05/03/sputum-microbiome-profiles-identify-severe-asthma-phenotypes-of-relative-stability-at-12-18-months/
..Data were available for 100 severe asthma subjects (median age: 55 yrs, 42% males). Two microbiome-driven clusters were identified, characterized by differences in asthma onset, smoking status, residential locations, percentage of blood and/or sputum neutrophils and macrophages, lung spirometry, and concurrent asthma medications (all p-values <.05). Cluster 2 patients displayed a commensal-deficient bacterial profile which was associated with worse asthma outcomes compared to cluster 1. …
https://2medical.news/2020/05/03/sputum-microbiome-profiles-identify-severe-asthma-phenotypes-of-relative-stability-at-12-18-months/
..Data were available for 100 severe asthma subjects (median age: 55 yrs, 42% males). Two microbiome-driven clusters were identified, characterized by differences in asthma onset, smoking status, residential locations, percentage of blood and/or sputum neutrophils and macrophages, lung spirometry, and concurrent asthma medications (all p-values <.05). Cluster 2 patients displayed a commensal-deficient bacterial profile which was associated with worse asthma outcomes compared to cluster 1. …
Associations of #sleep duration with patient-reported outcomes and healthcare use in U.S. adults with #asthma
https://2medical.news/2020/05/20/associations-of-sleep-duration-with-patient-reported-outcomes-and-healthcare-use-in-u-s-adults-with-asthma/
..Asthma was identified by self-report. Habitual hours of sleep duration were categorized as short (≤5), normal (6-8), and long (≥9). Multivariate regression analyses were used to examine the associations between sleep duration and patient-reported outcomes and healthcare use. Results Of the 1389 adults with asthma, 26% reported short sleep duration, 66% reported normal sleep duration, and 8% reported long sleep duration. Those with short sleep …
https://2medical.news/2020/05/20/associations-of-sleep-duration-with-patient-reported-outcomes-and-healthcare-use-in-u-s-adults-with-asthma/
..Asthma was identified by self-report. Habitual hours of sleep duration were categorized as short (≤5), normal (6-8), and long (≥9). Multivariate regression analyses were used to examine the associations between sleep duration and patient-reported outcomes and healthcare use. Results Of the 1389 adults with asthma, 26% reported short sleep duration, 66% reported normal sleep duration, and 8% reported long sleep duration. Those with short sleep …
Multimorbidity in #asthma, association with allergy, inflammatory markers and symptom burden, results from the Swedish GA2LEN study
https://2medical.news/2020/10/19/multimorbidity-in-asthma-association-with-allergy-inflammatory-markers-and-symptom-burden-results-from-the-swedish-ga2len-study/
..Subjects with asthma, rhinitis and eczema were more likely to be sensitised to seasonal allergens (67 vs 32%, p<0.001), food allergens (54 vs. 18%, p<0.001) and to have a higher degree of sensitisation than subjects with only asthma (23 vs 10%, p<0.001). Subjects with allergic multimorbidity more often had allergic reactions to food (28 vs 10%, p=0.002), more respiratory symptoms and anxiety/depression (40% vs, 14%, …
https://2medical.news/2020/10/19/multimorbidity-in-asthma-association-with-allergy-inflammatory-markers-and-symptom-burden-results-from-the-swedish-ga2len-study/
..Subjects with asthma, rhinitis and eczema were more likely to be sensitised to seasonal allergens (67 vs 32%, p<0.001), food allergens (54 vs. 18%, p<0.001) and to have a higher degree of sensitisation than subjects with only asthma (23 vs 10%, p<0.001). Subjects with allergic multimorbidity more often had allergic reactions to food (28 vs 10%, p=0.002), more respiratory symptoms and anxiety/depression (40% vs, 14%, …