American Thoracic Society

Stricter Clean Air Standards in U.S. Could Save Thousands of Lives

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Californians would benefit most from lower emissions

Adopting more rigorous standards for ambient air pollution would prevent roughly 6,000 deaths and 15,000 serious illnesses from occurring each year in the nation’s most polluted cities, according to a new report from the American Thoracic Society and New York University’s Marron Institute.

The second annual Health of the Air report estimates the health impact of adopting the American Thoracic Society (ATS) standards for key measures of air quality, which are lower than the standards currently adopted by the Environmental Protection Agency (EPA).

Specifically, the ATS calls for a 8-hour ground-level ozone (O3) standard of 0.060 ppm, instead of the EPA’s 0.070 ppm, and an annual fine particulate matter (PM2.5) standard of 11 μg/m3.

The report, published Feb. 8 in the journal Annals of ATS, found that 82% of monitored counties in the U.S. failed to meet the ATS standard for O3 during the 2013-2015 time period studied, while 8% failed to meet the ATS standard for PM2.5.

One in five (21%) monitored counties also failed to meet the ATS’s standard for 24-hour PM2.5 of 25 μg/m3.

Using air quality data that have been updated since the first report was published in 2016, the researchers estimated that 3,160 excess annual deaths (95% CI, 69-7,100) were associated with O3 concentrations greater than ATS-recommended standards. An estimated additional 3,100 excess deaths (95% CI, 2,100-4,100) were associated with PM2.5 concentrations greater than ATS recommendations.

Among the other findings:

  • The annual number of excess morbidities (including lung cancer incidence) attributable to O3 and PM2.5 exceeding ATS recommendations are approximately 8,760 (95% CI, -17,700-35,700) and 6,710 (95% CI, 1,980-11,300), respectively.
  • The total numbers of adversely impacted days attributable to O3 and PM2.5 concentrations above ATS recommendations are approximately 10,300,000 (95% CI, 2,490,000–20,600,000) and 2,420,000 (95% CI, 1,980,000– 2,840,000), respectively.
  • Central estimates indicated that O3 and PM2.5 generally contributed approximately equally to excess deaths and morbidities, whereas O3 was responsible for the majority of adversely impacted days.

The report highlighted the metropolitan areas that would have benefited the most between 2013-2015 from meeting the ATS O3 and PM2.5 standards, with Los Angeles taking the top spot — with an estimated 941 lives saved and 1,670 fewer morbidities.

Riverside, Calif. ranked second (609 lives saved, 1,250 fewer morbidities), followed by Bakersfield, Calif. (369 lives saved and 513 fewer morbidities), Fresno, Calif. (244 lives saved and 458 fewer morbidities), Pittsburgh (205 lives save and 382 fewer morbidities), Phoenix, Ariz. (178 lives saved and 432 fewer morbidities).

“These high population, high pollution areas see the most health effects from air pollution, and, as a result, they have the most to gain by reducing these emissions,” researcher Kevin R. Cromar, PhD, of New York University’s Marron Institute of Urban Management, told MedPage Today.

The Trump administration has vowed to do away with a host of federal regulations aimed at improving air quality, and last month the EPA, under director Scott Pruitt, announced close to 70 “deregulatory actions” linked to air quality that have been rolled back or are under review.

Cromar says despite these efforts, he is optimistic that air quality will continue to improve if local governments step up.

“If the expectation is that local governments won’t act until the federal government and EPA tells them to, then people may be disappointed in the near term,” he said. “But cities have all the authority they need to act, and this report gives them information about what they can expect to gain in terms of the health of their residents by improving air quality.”

Shorter Antibiotic Courses Recommended for HAP and VAP

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Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP)—which account for 20% to 25% of hospital-acquired infections—should be treated with shorter courses of antibiotics, according to new guidelines released by the Infectious Diseases Society of America and American Thoracic Society .

The new guidelines recommend seven days or less of antibiotics for most of these infections, which reflects a change from previous guidelines, which had recommended longer courses. The guidelines said the shorter courses ensure safe and effective treatment while limiting the development of antibiotic resistance.

The new guidelines also recommend that each hospital develop an antibiogram, a regular analysis of the strains of bacteria causing pneumonia locally as well as which antibiotics effectively treat them. When possible, the antibiogram should be specific to the hospital’s ICU patients, according to the guidelines. Antibiograms should be updated regularly, and the most appropriate frequency should be determined by the institution, the guidelines noted.

“Once clinicians are updated regularly on what bugs are causing VAP and HAP in their hospitals as well as their sensitivities to specific antibiotics, they can choose the most effective treatment,” said Andre C. Kalil, MD, MPH, a professor of medicine in the Division of Infectious Diseases and the director of the transplant infectious diseases program at the University of Nebraska Medical Center, in Omaha. “This helps individualize care, ensuring patients will be treated with the correct antibiotic as soon as possible.”

Published in 2005, the previous guidelines recommended different lengths of treatment time for antibiotic therapy based on the bacterium causing the infection. The 2016 guidelines recommend seven days or less for all bacteria. Newer evidence suggests that the shorter course of treatment does not reduce the benefits of therapy; in addition, this can reduce antibiotic-related side effects, the risk for Clostridium difficile, antibiotic resistance and costs, said Dr. Kalil, who also is a co-chair of the panel. In some cases, such as when a patient doesn’t improve or worsens, longer treatment may be necessary.

One of every 10 patients on a ventilator gets VAP, which is fatal about 13% of the time. VAP also increases:

  • the amount of time patients remain on a ventilator (7.6-11.5 days on average); and
  • the hospital length of stay (11.5-13.1 days on average).

While HAP typically is a less severe infection, half of patients have serious complications, including respiratory failure, pleural effusion, septic shock and kidney failure.

The guidelines panel featured experts from around the globe including infectious disease, pulmonary and critical care specialists; surgeons; pharmacologists; microbiologists; professional librarians; and methodologists.

BMJ to ban research funded by the tobacco industry

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The tobacco industry has been shown to mislead with its research, but is forcing it to become more hidden a better option?

woman with an e-cigarette

The BMJ‘s ban on Big Tobacco-funded research could harm work on e-cigarettes. Photograph: Alamy

Last week, the BMJ announced that it was finally implementing a practice that it had been discussing since the mid 1990s. Research partly or fully funded by the tobacco industry will no longer be published in BMJ, BMJ Open, Thorax and Heart.

This brings the journal in line with its own Tobacco Control journal, as well as a number of other publications, including PLoS Medicine, PLoS One, PLoS Biology and the Journal of Health Psychology.

It’s a turnaround for the BMJ, who published an editorial criticising the American Thoracic Society when it brought in the policy in 1996. It started a debate at the time, and since then, more and more evidence has shown that the tobacco industry has deliberately skewed scientific knowledge by presenting findings in a misleading way, withholding certain findings, and promoting false evidence of doubt in the scientific consensus about the harms of tobacco.

Not only that, internal documents have revealed this practice is still very much alive today, with memos earlier this year coming to light detailing a campaign to “ensure that PP (plain, or standardised packaging) is not adopted in the UK“.

While a lot of public health researchers are delighted by this news, even feeling that the BMJ are late to the game in implementing these restrictions, some are more worried by this censorship. Consider electronic cigarettes as an example. Nicoventures is in the process of developing the first MHRA-approved approximation of an e-cigarette (its device is not technically an e-cigarette, but is similar).
The company is running trials on the product at the moment. But though Nicoventures is a stand-alone company, it is owned by British American Tobacco. Under these new rules, it will not be able to publish its results in any of these journals.

At the moment e-cigarettes are unregulated, so current knowledge of their potential harms and benefits, is based on anecdote and speculation rather than data. As tobacco companies buy up e-cigarettes companies, this will make researching their efficacy as a nicotine replacement therapy difficult or potentially even impossible. Already there are plans to regulate them as a medical product, which may mean they could be removed from sale until they had been properly tested.

I personally believe this would be a poor decision; although we are unsure of the long-term harms resulting from the use of these devices, it’s practically inconceivable that they will be more harmful than smoking cigarettes, and will likely be considerably less so. Given the tales of hardened smokers finding them an effective replacement for cigarettes, removing them from the market may well result in a lot of people going back to smoking, which would be a negative outcome.

Finally, as we already know from the work of people like Ben Goldacre, a big problem in medical literature is the selective withholding of data by those with vested interests. Not just the tobacco industry, but the pharmaceutical industry as well.

Goldacre calls for regulations that would force all this unpublished data to be made public, rather than for banning pharma from funding research. Perhaps it’s a slightly different issue, since pharma are creating products to cure, whereas the tobacco industry creates a product that kills. But ultimately, both are businesses, primarily concerned with making money.

Might banning the tobacco industry from funding work to be published in these journals lead to it adopting worse practices, and actively obscuring its role in funding research? At the moment, declaration of financial support is essentially an honour system. There’s not really anything beyond integrity stopping a researcher from simply not disclosing who funded research. If tobacco companies deliberately obscure their involvement with research, we would be in an even worse situation, where we as scientists would not know if research had a higher chance of bias due to the involvement of the tobacco industry.

Dupilumab in Persistent Asthma with Elevated Eosinophil Levels.

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BACKGROUND

Moderate-to-severe asthma remains poorly treated. We evaluated the efficacy and safety of dupilumab (SAR231893/REGN668), a fully human monoclonal antibody to the alpha subunit of the interleukin-4 receptor, in patients with persistent, moderate-to-severe asthma and elevated eosinophil levels.

METHODS

We enrolled patients with persistent, moderate-to-severe asthma and a blood eosinophil count of at least 300 cells per microliter or a sputum eosinophil level of at least 3% who used medium-dose to high-dose inhaled glucocorticoids plus long-acting beta-agonists (LABAs). We administered dupilumab (300 mg) or placebo subcutaneously once weekly. Patients were instructed to discontinue LABAs at week 4 and to taper and discontinue inhaled glucocorticoids during weeks 6 through 9. Patients received the study drug for 12 weeks or until a protocol-defined asthma exacerbation occurred. The primary end point was the occurrence of an asthma exacerbation; secondary end points included a range of measures of asthma control. Effects on various type 2 helper T-cell (Th2)–associated biomarkers and safety and tolerability were also evaluated.

RESULTS

A total of 52 patients were assigned to the dupilumab group, and 52 patients were assigned to the placebo group. Baseline characteristics were similar in the two groups. Three patients had an asthma exacerbation with dupilumab (6%) versus 23 with placebo (44%), corresponding to an 87% reduction with dupilumab (odds ratio, 0.08; 95% confidence interval, 0.02 to 0.28; P<0.001). Significant improvements were observed for most measures of lung function and asthma control. Dupilumab reduced biomarkers associated with Th2-driven inflammation. Injection-site reactions, nasopharyngitis, nausea, and headache occurred more frequently with dupilumab than with placebo.

CONCLUSIONS

In patients with persistent, moderate-to-severe asthma and elevated eosinophil levels who used inhaled glucocorticoids and LABAs, dupilumab therapy, as compared with placebo, was associated with fewer asthma exacerbations when LABAs and inhaled glucocorticoids were withdrawn, with improved lung function and reduced levels of Th2-associated inflammatory markers.

Source: NEJM

 

 

 

 

 

Mannose-binding lectin and innate immunity in bronchiectasis.

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Pathogenic microorganisms often thrive in the inflammatory milieu of the bronchiectatic airway where innate and adaptive defence mechanisms can be impaired. Although genetic defects of the adaptive immune system causing immunodeficiency syndromes are well characterised, genetic defects that impair the recognition of microbes by the innate immune system have only recently been identified.1 For example, polymorphisms in the gene for mannose-binding lectin (MBL), a receptor of the innate immune system that recognises microbial carbohydrates, can lead to deficiency of MBL and increased susceptibility to infection.

When the lungs are exposed to a new pathogen, the first line of defence is the innate immune system, which results in a swift and semi-specific response. Cells of the innate immune system, which include dendritic cells and macrophages, recognise highly conserved structures called pathogen-associated molecular patterns (PAMPs) that are shared by large groups of microorganisms. PAMPs are recognised by pattern-recognition receptors, which activate the cells of the innate immune system to rapidly attack and kill microbes.2

MBL is a soluble pattern-recognition receptor that is synthesised in the liver and is released into the systemic circulation as a component of the acute-phase response. It is not produced locally in the lungs and is thought to leak into the airways and alveoli from the systemic circulation, particularly in the presence of inflammation.3 MBL binds to various respiratory pathogens including Haemophilus influenzae and Pseudomonas aeruginosa, which are commonly identified in the airways of patients with bronchiectasis, and enhances the killing of these organisms by activation of the lectin complement pathway and by facilitating phagocytosis by opsonisation.4

In The Lancet Respiratory Medicine, James Chalmers and colleagues report a large, prospective study5 assessing the relation between MBL deficiency and clinical outcomes during a 4 year follow-up of patients with non-cystic fibrosis bronchiectasis. 55 (12%) of 470 patients with bronchiectasis had genotypes associated with MBL deficiency. These patients had more frequent exacerbations and were more likely to be chronically colonised with bacteria, particularly by P aeruginosa, than were patients with genotypes not associated with MBL deficiency. One strength of the study was the measurement of both MBL deficient genotypes and serum concentrations, which were strongly correlated. Serum MBL deficiency (<200 ng/mL) was also associated with increased exacerbation frequency.

The results of Chalmers and colleagues’ study5 are consistent with the findings from studies of patients with cystic fibrosis in which MBL deficiency has been associated with increased severity of disease. In patients with cystic fibrosis, MBL deficiency results in earlier acquisition of P aeruginosa, reduced pulmonary function, and increased mortality.6 However, a retrospective study7 of patients with non-cystic fibrosis bronchiectasis reported no association between low MBL concentrations and exacerbation frequency. Several conflicting results have also been published from studies8 assessing the association between low levels of MBL and acute exacerbations of chronic obstructive pulmonary disease.

What are the clinical implications of Chalmers and colleagues’ study? The study provides evidence that MBL deficiency is a new risk factor for infection and acute exacerbations in patients with non-cystic fibrosis bronchiectasis. Identification of patients at high risk of development of severe disease could direct clinicians to undertake more intensive management and follow-up of these patients with a view to reducing rates of hospital admission and mortality. Such stratification is increasingly relevant because of the growing range of treatments that is emerging for bronchiectasis. These treatments include long-term azithromycin, nebulised gentamicin, inhaled mannitol, inhaled dry powder ciprofloxacin, and nebulised liposomal ciprofloxacin. Recombinant human MBL might also become a treatment option, after it was reported in a phase 1 study9 to be safe, well tolerated, and able to restore activity of the lectin pathway of complement.

A standard definition of clinically significant MBL deficiency is not presently available but a diagnostic approach that incorporates both serum concentrations and genotyping seems sensible. Some patients with genotypes that are not associated with deficiency can still have very low MBL serum concentrations and, alternatively, serum concentrations can increase with the acute-phase response. One pragmatic approach analogous to that recommended by the American Thoracic Society and European Respiratory Society for α1-antitrypsin deficiency might be for clinicians to initially measure the serum concentration of MBL in patients with bronchiectasis. If the serum level is low, genotyping could then be undertaken. A cutoff of 200 ng/mL, as used in the study by Chalmers and colleagues, classified 19% of patients with bronchiectasis as MBL deficient. Better access to testing facilities and further studies are required to confirm the findings of the present study5before testing for MBL deficiency becomes routine practice in non-cystic fibrosis bronchiectasis. The present findings also raise some interesting questions for future research. MBL deficiency is relatively common in the general population and does not seem to predispose to an increased risk of infection in the absence of other predisposing factors. How do other predisposing factors interact with MBL deficiency to increase the risk of infection and cause severe disease or poor longitudinal outcomes in bronchiectasis? Could serial MBL concentrations in serum and sputum be used as markers for early detection of exacerbations or determination of the duration of antibiotic treatment? Does azithromycin interact with MBL to improve phagocytic activity in macrophages? Although some evidence suggests that azithromycin increases mannose receptor (a pattern-recognition receptor in the same family as MBL) expression and phagocytic activity in alveolar macrophages, the effect of azithromycin on MBL expression is unclear.

Source: lancet

bronchie

Asthma Linked To Menstrual Cycle; Hormones Affect Respiratory Symptoms In Women.

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A new study suggests that a woman’s menstrual cycle can affect respiratory symptoms, potentially exacerbating conditions such as asthma.

According to the BBC, Norwegian researchers studied thousands of women with regular menstrual cycles and found that respiratory symptoms became more severe around the time of ovulation.

“The effects of the menstrual cycle on respiratory symptoms in the general population have not been well studied,” said lead author Ferenc Macsali of Norway’s Haukeland University Hospital. “In a cohort of nearly 4,000 women, we found large and consistent changes in respiratory symptoms according to menstrual cycle phase, and, in addition, these patterns varied according to body mass index (BMI), asthma, and smoking status.”

Outcome Magazine summarized the findings:

Significant variations over the menstrual cycle were found for each symptom assessed in all subjects and subgroups. Reported wheezing was higher on cycle days 10-22, with a mid-cycle dip near the putative time of ovulation (~days 14-16) in most subgroups.

Shortness of breath was highest on days 7-21, with a dip just prior to mid-cycle in a number of subgroups. The incidence of cough was higher just after putative ovulation for asthmatics, subjects with BMI ≥ 23kg/m2, and smokers, or just prior to ovulation and the onset of menses in subgroups with a low incidence of symptoms.

The BBC notes that “of those studied, 28.5 percent were smokers and 8 percent had been diagnosed with asthma.”

The study was published online Nov. 9 in the American Thoracic Society‘s American Journal of Respiratory and Critical Care Medicine.

“Our finding that respiratory symptoms vary according to the stage of the menstrual cycle is novel, as is our finding that these patterns vary according to BMI and smoking status,” Macsali said in a journal news release, according to HealthDay News. “These relationships indicate a link between respiratory symptoms and hormonal changes through the menstrual cycle.”

Macsali added that the results may help women with asthma better manage their symptoms.

“Our results point to the potential for individualizing therapy for respiratory diseases according to individual symptom patterns,” he said. “Adjusting asthma medication, for example, according to a woman’s menstrual cycle might improve its efficacy and help reduce disability and the costs of care.”

Dr. Samantha Walker of charity Asthma UK concurred.

“This research is really interesting, and could help women with asthma to manage their condition better,” Walker told the BBC. “Asthma can be triggered by many different things, and this varies from person to person — but we always encourage people with asthma to be aware of things that trigger their symptoms so that they can take steps to control them.

Though this study may be “novel” in its findings, it would not be the first to find a link between a woman’s menstrual cycle and changes in asthma symptoms.

In 1996, the New York Times reported that a study published in the Archives of Internal Medicine had provided evidence to support this connection.

The study, which had looked at the menstrual phase of 182 female patients who needed emergency-room treatment for asthma at hospitals in Pennsylvania, found that “hormonal changes that occur as menstruation starts may make some asthmatic women more vulnerable to attacks.” Specifically, researchers found that 20 percent of the patients were preovulatory and 24 percent were in the ovulatory phase when the attacks occurred.

The Times also pointed out that the possibility of such a link had been first reported in a medical journal in 1931, though it was a connection that had “never been proved or studied extensively” before.

According to statistics provided by the Asthma and Allergy Foundation of America, nearly 25 million Americans suffer from asthma and more than 3,300 die from the condition every year. The condition is also said to be more prevalent among adult women than men.