COPD World News
COPD World News - Week of November 18, 2018
Physical activity characteristics in COPD, bronchiectasis and asthma
Newcastle, NSW, Australia – A study recently published in the journal Respirology looked at differences in physical activity in three obstructive airway diseases – COPD, asthma and bronchiectasis. Physical activity (PA) in obstructive airway diseases (OAD) is likely to be impaired but this has not been extensively studied outside of chronic obstructive pulmonary disease (COPD). The researchers describe physical activity levels in severe asthma and bronchiectasis compared to moderate-severe COPD and to controls, and tested the cross-sectional associations of physical activity (steps/day) with shared disease characteristics in the obstructive airway diseases group. Adults with OAD (severe asthma = 62, COPD = 67, bronchiectasis = 60) and controls (n = 63) underwent a multidimensional assessment, including device-measured physical activity levels. The OAD group included 189 participants (58.7% females), with median (interquartile range) age of 67 (58-72) years and mean forced expiratory volume in the first second (FEV1) % predicted of 69.4%. Demographic characteristics differed between groups. Compared to controls (52.4% females, aged 55 (34-64) years, median 7640 steps/day), those with severe asthma, bronchiectasis and COPD accumulated less steps/day: median difference of -2255, -2289, and -4782, respectively (P ≤ 0.001). Compared to COPD, severe asthma and bronchiectasis participants accumulated more steps/day: median difference of 2375 and 2341, respectively (P ≤ 0.001). No significant differences were found between the severe asthma and bronchiectasis group. Exercise capacity, FEV1 % predicted, dyspnoea and systemic inflammation differed between groups, but were each significantly associated with steps/day in OAD. In the multivariable model adjusted for all disease characteristics, exercise capacity and FEV1 % predicted remained significantly associated. The researchers concluded that physical activity impairment is common in obstructive airway diseases. The activity level was associated with shared characteristics of these diseases. Interventions to improve physical activity should be multifactorial and consider the level of impairment and the associated characteristics.
For more information: https://www.ncbi.nlm.nih.gov/m/pubmed/30384396/?i=1&from=copd
COPD World News - Week of November 11, 2018
The 1918 Flu Pandemic: Informing influenza research, 100 years later
Winnipeg, MB - Worldwide, the 1918 Spanish Flu pandemic swiftly killed approximately 50 million people and infected millions more – approximately 1/3 of the world’s population. This pandemic was particularly unpredictable because it impacted otherwise healthy adults the most. The mortality rate among this group was 20 times greater than with the seasonal flu. Physicians could offer very little in the way of prevention or treatment – the most common prescription was bed rest and a careful diet. Many Canadians only think of the flu in the fall, especially when they are reminded to get their flu shots. However, dedicated scientists at the Public Health Agency of Canada’s National Microbiology Laboratory (NML) still refer to the memory of the 1918 flu in their day-to-day work. This is because the 1918 flu pandemic is sometimes called the “mother of all human flu viruses”. In fact, almost all cases of influenza A have been caused by flu viruses that can be genetically traced back to the 1918 flu. No one knows for sure where on the map the 1918 virus actually came from, but Dr. Darwyn Kobasa, a scientist at the NML, agrees that like all other flu viruses, it likely originated in a bird. However, in order for the virus to make the jump from birds to human, it needed an intermediate host to allow the transmission to humans .“Beginning as an avian virus,” Dr. Kobasa describes, “the 1918 virus most likely crossed into mammal hosts—possibly to pigs first, and then to humans—after an unknown period of adaptation.” “This period of adaptation,” he explained, “is one of the events that many flu researchers are now looking for with avian viruses—that is, mutations that would support a cross-over event to a new host species from birds.” NML scientists found that the virus was very unique, even among the most severe strains of the human flu. In fact, when NML scientists needed to work with the 1918 flu virus directly, they could only do so in a level four containment lab. These state-of-the-art, high security laboratories are where scientists investigate deadly pathogens under the most secure conditions possible, in order to keep themselves and others safe from the virus. Today, NML scientists are on the lookout for signs in current avian viruses that could possibly mutate and lead to a virus with the potential of causing another severe pandemic outbreak. The world has seen several flu pandemics, including in 1957-1958, 1968-1969 and 2009-2010, but none were as severe as the 1918 pandemic. Canadian researchers at the NML played a crucial role in decoding the 2009-2010 pandemic flu virus, isolating and replicating certain genes in the virus. Thanks to scientists, like those at the NML, the world has made incredible progress through the use of flu vaccines and treatments which have helped to prevent and treat the severity of infections and diseases. Public health is in the hands of us all, and getting your flu shot is the best way to keep you and your family safe during flu season. The 1918 flu pandemic remains a warning of what could happen if a completely new flu virus were to appear in the future. However, we have learned throughout history that no two pandemics are identical – we must be ready to adapt and adjust our public health advice based on situations as they develop.
For more information: http://www.science.gc.ca/eic/site/063.nsf/eng/97681.html
COPD World News - Week of November 4, 2018
Study suggests heart attack more likely after flu
Toronto, ON – A recent study led by researchers at the University of Toronto and published in the New England Journal of Medicine, looked at seven years of data, sifting through nearly 20,000 Ontario adult cases of laboratory-confirmed influenza infection from 2009 to 2014. They identified 364 patients with confirmed cases of the flu within a year before or after having a heart attack. The study indicates that one is six times more likely to have a heart attack after the flu than usual. Of these cases, 20 heart attacks happened in the single week after a flu diagnosis, compared to 344 (just 3.3 admissions per week) during the rest of the year. Severe cases of the flu are a shock to the entire system. The resulting inflammation can make the heart beat faster, and it can also activate platelets that then increase the odds that blood will clot in the arteries that serve the heart. The team also looked at other confirmed acute respiratory infections, such as respiratory syncytial virus (RSV) or non-viral infections. Although heart attack risk was also elevated to triple their normal incidence, flu infections saw the most significant association. “Our findings, combined with previous evidence that influenza vaccination reduces cardiovascular events and mortality, support international guidelines that advocate for influenza immunization in those at high risk of heart attacks,” said epidemiologist and lead author Jeff Kwong in a statement. An unconfirmed link between the flu and heart attacks was first noted in the 1930s. However, many studies did not definitively prove flu infection (versus other similar acute respiratory infections), or were designed in ways that could have given biased results. This confirmation is important for many reasons. It adds to the growing evidence that the annual flu shot is important for everyone who is medically able to get it – not just because the flu itself is deadly, but because of the potential complications. This is especially true for patients already at increased risk of heart disease. It also emphasizes the importance that patients go for medical evaluation without delay if they experience heart symptoms, like chest pain or shortness of breath, within the first week of an acute respiratory infection. People should also take standard precautions, like frequent handwashing and keeping distance from people with the flu.
For more information: https://www.nejm.org/doi/full/10.1056/NEJMoa1702090
For more information: https://www.nejm.org/doi/full/10.1056/NEJMoa1702090
COPD World News - Week of October 28, 2018
Respiratory health should be studied on migrant and refugee populations
Washington, DC - Migrants represent a diverse population comprising workers, students, undocumented individuals, and refugees. Worldwide, approximately 1 billion people were considered migrants in 2016. Notably, about 65 million of these migrants were forcibly displaced from their homes, and 20 million were considered refugees. While the geopolitical consequences of such migration continue to be considered, less is known about the impact of these events on the respiratory health of migrants and refugees. In recognition of this knowledge gap, the American Thoracic Society and the European Respiratory Society brought together investigators with diverse and relevant expertise to participate in a workshop and develop a consensus on research needs on the respiratory health of migrants and refugees. The workshop focused on environmental and occupational hazards, chronic noninfectious diseases, and respiratory infectious diseases, which were presented by experts in three distinct sessions, each culminating with panel discussions. A writing committee collected summaries prepared by speakers and other participants, and the information was collated into a single document. Recommendations were formulated, and differences were resolved by discussion and consensus. The group identified important areas of research need, while emphasizing that reducing the burden of pulmonary, critical care, and sleep disorders in migrants and refugees will require a concerted effort by all stakeholders. Using best research practices, considering how research impacts policies affecting migrant and refugee populations, and developing new approaches to engage and fund trainees, clinical investigators, and public health practitioners to conduct high-quality research on respiratory health of migrants and refugees is essential.
For more information: https://www.ncbi.nlm.nih.gov/pubmed/30382778
COPD World News - Week of October 21, 2018
Long-term trial of “Urban Training” to increase physical activity in patients with COPD
Barcelona, Spain -There is a need to increase and maintain physical activity in patients with chronic obstructive pulmonary disease (COPD). Researchers here assessed 12-month efficacy and effectiveness of the Urban Training intervention on physical activity in COPD patients. This randomised controlled trial (NCT01897298) allocated 407 COPD patients from primary and hospital settings 1:1 to usual care (n=205) or Urban Training (n=202). Urban Training consisted of a baseline motivational interview, advice to walk on urban trails designed for COPD patients in outdoor public spaces and other optional components for feedback, motivation, information and support (pedometer, calendar, physical activity brochure, website, phone text messages, walking groups and a phone number). The primary outcome was 12-month change in steps·day−1measured by accelerometer. Efficacy analysis (with per-protocol analysis set, n=233 classified as adherent to the assigned intervention) showed adjusted (95% CI) 12-month difference +957 (184–1731) steps·day−1between Urban Training and usual care. Effectiveness analysis (with intention-to-treat analysis set, n=280 patients completing the study at 12 months including unwilling and self-reported non-adherent patients) showed no differences between groups. Leg muscle pain during walks was more frequently reported in Urban Training than usual care, without differences in any of the other adverse events. Urban Training, combining behavioral strategies with unsupervised outdoor walking, was efficacious in increasing physical activity after 12 months in COPD patients, with few safety concerns. However, it was ineffective in the full population including unwilling and self-reported non-adherent patients.
For more information: http://erj.ersjournals.com/content/52/4/1800063?ctkey=shareline
COPD World News - Week of October 14, 2018
Impotence warnings might motivate men to kick the habit
San Antonio, TX - Most men who smoke cigarettes are very aware that the habit increases their risk for lung cancer, chronic obstructive pulmonary disease (COPD), and heart disease. But a small study suggests they are largely unaware of another smoking-related risk, one that hits below the belt, Khushbir Bath, MD, of Harlem Hospital in New York City, reported here. When clinicians at Bath's hospital asked over 100 men (current or former smokers) if they knew that smoking is a risk factor for erectile dysfunction, fewer than one in seven said they did. The finding, if confirmed in larger studies, suggests that anti-tobacco public health messaging may be missing an opportunity to motivate men to kick the habit, Bath told MedPage Today. The study was presented at CHEST 2018, the annual meeting of the American College of Chest Physicians. "If more men knew that smoking for 20 or 30 years increases their risk of having difficulty achieving an erection, that could be a strong motivator for quitting," he said. "Maybe even more of a motivator for some men than telling them, 'You are going to die.'" Bath said he got the idea for the study after having a conversation with a patient in his 40s who said he was having difficulty with erections. The man, who was a heavy smoker, said he wasn't aware the habit could contribute to erectile dysfunction. "He knew that smoking caused lung cancer, heart disease, and mouth cancer. He even knew that it caused infertility in women, but he didn't know that it caused difficulty with erections," Bath said. "When I told him he looked at me and said, 'I'm going to quit right now.'" Bath said the informal study included 104 men (>18 years) who smoked or were former smokers being treated at his Harlem Hospital primary care clinic who volunteered to take the survey. Questionnaires collected data on demographics, general health status, smoking history, past medical history, and knowledge regarding smoking and its health hazards. The majority of the respondents were African American (57%), and 23% were Hispanic. Most of the participants were current smokers (96%). Of those, 39% had smoked for over 20 years, 45% reported smoking more than a pack per day, and 97% reported that the main hazard of smoking is lung cancer, while 47% reported heart disease as likely to be related to smoking. Only 14 responders (13%) knew about the association between smoking and erectile dysfunction. All respondents said having adequate knowledge of the association between smoking and all three of these health conditions would be a motivator for them to quit smoking. Bath said that when he conducted an informal investigation, including an internet search, to examine cigarette package labeling and anti-tobacco messaging in the U.S., he found no mention of erectile dysfunction as a smoking-related risk. In contrast, he found that cigarette package labeling in 26 countries outside the U.S. included impotence warnings. Bath said countless studies over the past 20 years have proven the link between chronic cigarette smoking and impotence. He added that he would like to see a larger study done to confirm his findings. "From my small study it does appear that people in my community lack this knowledge," he said. "Primary care physicians should be telling their male patients who smoke about this risk."
For more information: https://tinyurl.com/yafc8u4c
COPD World News - Week of October 7, 2018
US Officials emphasize flu vaccination after 80K died last year
Washington, DC - Following a severe 2017-2018 influenza season in which an estimated 900,000 people were hospitalized and 80,000 died, United States officials reemphasized the need for everyone aged 6 months or older to get vaccinated. “Those 80,000 who died, guess what, they got that influenza from someone,” U.S. Surgeon General Jerome M. Adams, MD, MPH, said Thursday during the annual influenza news conference hosted by the National Foundation for Infectious Diseases (NFID). “It’s critically important that we impress upon folks. A projected 168 million doses of influenza vaccine that will be available this season. Adams said influenza caused 180 deaths in children last season “and the majority of them were not vaccinated.” The CDC believes 180 deaths is an underestimation because not all influenza-related deaths are reported. The study showed that the highest coverage was associated with workplace vaccination requirements and was consistently higher among health care personnel working in hospital settings. Influenza vaccination coverage among health care personnel working in long-term care settings remains consistently lower than all other settings — a concerning finding considering many of them work as assistants and aides to the elderly, who experience lower vaccine efficacy and are at increased risk for severe disease, the authors said. Additionally, older adults and those with certain chronic health conditions, such as heart and lung disease, diabetes and obesity, are at risk for serious influenza complications, according to NFID. Last season took the greatest toll on adults aged 65 years and older. According to the CDC, 70% of hospitalizations and 90% of deaths occurred in that age group. “Influenza is difficult to predict and can cause serious complications even for the healthy,” Adams said. “Vaccination is the best thing you can do to protect yourself, your family, and my family. Together, let’s fight flu.”
For more information: https://tinyurl.com/y83fes2l
COPD World News - Week of September 30, 2018
Smoking, not COPD, as the disease
Boston, MA - Smoking causes not only cancer but also cardiovascular diseases such as stroke, coronary heart disease, hypertension, thromboembolism, and peripheral artery disease, lung disease such as chronic obstructive pulmonary disease (COPD), and many other diseases, including (but not limited to) type 2 diabetes, rheumatoid arthritis, cataracts, and macular degeneration.1 These diseases develop with age and contribute in different measure to the current epidemic of chronic noncommunicable diseases that are associated with smoking and aging. Even though the effects of smoking are broad and devastating, much smoking-related research traditionally focuses on the lung because the lung is considered to be the primary target organ of smoking.3 Even though COPD is one of the major consequences of smoking, COPD usually does not exist by itself, because it is almost invariably associated with concomitant chronic respiratory and non-respiratory diseases that contribute to the clinical manifestations and severity of the smoking-induced systemic disease. COPD, as defined by the Global Initiative for Chronic Obstructive Lung Disease, is diagnosed as persistent airflow limitation in smokers. This definition has limitations for clinical practice, because it does not mention symptoms and applies only to smokers in whom airflow limitation has developed. In fact, the only COPD we know well is the one that is defined as airflow limitation in smokers, because most of the data available on the pathophysiology and management of COPD have been derived from smokers with airflow limitation that was defined according to spirometric assessment. Woodruff and colleagues report appeared in a recent issue the New England Journal of Medicine. Their report looked at a group of smokers with normal findings on spirometry who have chronic respiratory symptoms, exacerbations (identified as the use of antibiotic agents, systemic glucocorticoids, or both or an event of health care utilization such as an office visit, hospital admission, or emergency department visit for a respiratory flare-up), lower than normal exercise tolerance, and imaging evidence of bronchiolitis. Thus, they conclude that spirometry is not adequate to define the breadth of smoking-induced lung disease. These results confirm and extend the findings of another recent large study that showed that more than 50% of symptomatic smokers with normal findings on spirometry have considerable respiratory-related impairment and evidence of emphysema on imaging. Most of these symptomatic smokers with normal findings on spirometry are often treated (without any evidence) with inhaled bronchodilators and glucocorticoids — that is, they are treated like patients with COPD, but they do not have COPD according to our current definition. These two studies introduce an important paradigm shift in our approach to smoking-induced disease. Both studies show that patients who have chronic respiratory symptoms without airflow limitation have the same respiratory consequences as those who have mild-to-moderate airflow obstruction and get the official diagnostic label of COPD. This finding tells us that symptoms are at least as sensitive as airflow limitation in establishing a diagnosis of smoking-induced disease. The observation that bronchiolitis and emphysema that are detected by means of computed tomographic scanning may be present in some smokers without airflow limitation lends a firm biologic basis to these inferences and reminds us, once again, that COPD may be a disease of the “lung’s quiet zone,” as defined by Mead almost 50 years ago — a place where there can be pathobiologic changes that are not detected by changes in the forced expiratory volume in 1 second (FEV1). These two studies have identified a complex clinical syndrome that is treated as COPD in practice even when airflow limitation is not present — a syndrome that very much resembles heart failure without impairment of ejection fraction.
For more information: https://tinyurl.com/yc4d9hzz
COPD World News - Week of September 23, 2018
AI improves doctors’ ability to diagnose lung disease
Paris, France: Artificial intelligence (AI) can be an invaluable aid to help lung doctors interpret respiratory symptoms accurately and make a correct diagnosis, according to new research presented today (Wednesday) at the European Respiratory Society International Congress . Dr Marko Topalovic (PhD), a postdoctoral researcher at the Laboratory for Respiratory Diseases, Catholic University of Leuven (KU Leuven), Belgium, told the meeting that after training an AI computer algorithm using good quality data, it proved to be more consistent and accurate in interpreting respiratory test results and suggesting diagnoses than lung specialists. "Pulmonary function tests provide an extensive series of numerical outputs and their patterns can be hard for the human eye to perceive and recognise; however, it is easy for computers to manage large quantities of data like these and so we thought AI could be useful for pulmonologists. We explored if this was true with 120 pulmonologists from 16 hospitals. We found that diagnosis by AI was more accurate in twice as many cases as diagnosis by pulmonologists. These results show how AI can serve as a second opinion for pulmonologists when they are assessing and diagnosing their patients," he said. Pulmonary function tests (PFT) include: spirometry, which involves the patient breathing through a mouthpiece to measure the amount of air inhaled and exhaled; a body box or plethysmography test, which enables doctors to assess lung volume by measuring the pressure in a booth in which the patient is sitting and breathing through a mouthpiece; and a diffusion capacity test, which tests how well a patient's lungs are able to transfer oxygen and carbon dioxide to and from the bloodstream by testing the efficiency of the alveoli (small air sacks in the lungs). Results from these tests give doctors important information about the functioning of the lungs, but do not tell them what is wrong with the patient. This requires interpretation of the results in order to reach a diagnosis. In this study, the researchers used historical data from 1430 patients from 33 Belgian hospitals. The data were assessed by an expert panel of pulmonologists and interpretations were measured against gold standard guidelines from the European Respiratory Society and the American Thoracic Society. The expert panel considered patients' medical histories, results of all PFTs and any additional tests, before agreeing on the correct interpretation and diagnosis for each patient. "When training the AI algorithm, the use of good quality data is of utmost importance," explained Dr Topalovic. "An expert panel examined all the results from the pulmonary function tests, and the other tests and medical information as well. They used these to reach agreement on final diagnoses that the experts were confident were correct. These were then used to develop an algorithm to train the AI, before validating it by incorporating it into real clinical practice at the University Hospital Leuven. The challenging part was making sure the algorithm recognised patterns of up to nine different diseases." Then, 120 pulmonologists from 16 European hospitals (from Belgium, France, The Netherlands, Germany and Luxembourg) made 6000 interpretations of PFT data from 50 randomly selected patients. The AI also examined the same data. The results from both were measured against the gold standard guidelines in the same way as during development of the algorithm. The researchers found that the interpretation of the PFTs by the pulmonologists matched the guidelines in 74% of cases (with a range of 56-88%), but the AI-based software interpretations perfectly matched the guidelines (100%). The doctors were able to correctly diagnose the primary disease in 45% of cases (with a range of 24-62%), while the AI gave a correct diagnosis in 82% of cases. Dr Topalovic said: "We found that the interpretation of pulmonary function tests and the diagnosis of respiratory disease by pulmonologists is not an easy task. It takes more information and further tests to reach a satisfactory level of accuracy. On the other hand, the AI-based software has superior performance and therefore can provide a powerful decision support tool to improve current clinical practice. Feedback from doctors is very positive, particularly as it helps them to identify difficult patterns of rare diseases." Two large Belgian hospitals are already using the AI-based software to improve interpretations and diagnoses. "We firmly believe that we can empower doctors to make their interpretations and diagnoses easier, faster and better. AI will not replace doctors, that is certain, because doctors are able to see a broader perspective than that presented by pulmonary function tests alone. This enables them to make decisions based on a combination of many different factors. However, it is evident that AI will augment our abilities to accomplish more and decrease chances for errors and redundant work. The AI-based software has superior performance and therefore may provide a powerful decision support tool to improve current clinical practice. "Nowadays, we trust computers to fly our planes, to drive our cars and to survey our security. We can also have confidence in computers to label medical conditions based on specific data. The beauty is that, independent of location or medical coverage, AI can provide the highest standards of PFT interpretation and patients can have the best and affordable diagnostic experience. Whether it will be widely used in future clinical applications is just a matter of time, but will be driven by the acceptance of the medical community," said Dr Topalovic. He said the next step would be to get more hospitals to use this technology and investigate transferring the AI technology to primary care, where the data would be captured by general practitioners (GPs) to help them make correct diagnoses and referrals. Professor Mina Gaga is President of the European Respiratory Society, and Medical Director and Head of the Respiratory Department of Athens Chest Hospital, Greece, and was not involved in the study. She said: "This work shows the exciting possibilities that artificial intelligence offers to doctors to help them provide a better, quicker service to their patients. Over the past 20 to 30 years, the evolution in technology has led to better diagnosis and treatments: a revolution in imaging techniques, in molecular testing and in targeted treatments have make medicine easier and more effective. AI is the new addition! I think it will be invaluable in helping doctors and patients and will be an important aid to their decision-making."
For more information: https://tinyurl.com/yckg8vb9
COPD World News - Week of September 16, 2018
Low dose aspirin bombs again for primary prevention
Melbourne, Australia - MedPage Today reported that daily aspirin not only failed to help generally healthy older individuals reduce their risk of disability-free survival and cardiovascular disease in the placebo-controlled ASPREE trial, it also appeared to raise overall mortality and particularly death from cancer. The primary endpoint of combined death, dementia, persistent physical disability came up in equal rates among healthy seniors randomized to 100 mg daily enteric-coated aspirin or placebo for 5 years (21.5 versus 21.2 events per 1,000 person-years, HR 1.01, 95% CI 0.92-1.11), according to ASPREE investigators led by John J. McNeil, MD, of Monash University in Australia. Major hemorrhages were found to be more common in the aspirin group (8.6 versus 6.2 per 1,000 person-years, HR 1.38, 95% CI 1.18-1.62). This counted the uptick in upper GI bleeding (HR 1.87, 95% CI 1.32-2.66) and intracranial bleeds (HR 1.50, 95% CI 1.11-2.02). Aspirin users also showed a higher risk of all-cause mortality (12.7 versus 11.1 per 1,000 person-years, HR 1.14, 95% CI 1.01-2.19), which was driven by cancer deaths (6.7 versus 5.1 per 1,000 person-years, HR 1.31, 95% CI 1.10-1.56). "The trial was terminated at a median of 4.7 years of follow-up after a determination was made that there would be no benefit with continued aspirin use with regard to the primary end point," the authors noted in a report published online in the New England Journal of Medicine (one of three covering various aspects of the trial). No individual component of the primary endpoint made a case for the benefit of aspirin, which failed to reduce the risk of cardiovascular disease as well (10.7 versus 11.3 events per 1,000 person-years, HR 0.95, 95% CI 0.83-1.08). "Interpretation of these results should take into account the lower-than-expected rate of cardiovascular disease among the trial participants ... most likely reflecting the relatively good health of the participant population at recruitment and the declining rate of cardiovascular disease in the two countries over time and across all age groups," the investigators suggested. Steven Nissen, MD, of Cleveland Clinic, said that the main results of ASPREE are not surprising. "Many people, including me, do not believe that aspirin offers meaningful benefits in primary prevention and carries substantial bleeding risks ... Unless the cardiovascular risk is very high (>20% over ten years), prophylactic aspirin results in more harm than good." The trial follows in the heels of other major studies offering mixed-to-negative data on aspirin for primary prevention, most recently ASCEND and ARRIVE in diabetes and moderate-risk patients, respectively (both were recently presented at the European Society of Cardiology meeting). ASPREE was a 19,114-person study of low-dose aspirin conducted in Australia and the U.S. McNeil and colleagues noted that adherence to the assigned treatment was 62.1% and 64.1% among aspirin and placebo recipients, respectively, during the final year of trial participation. Participants had to be 70 years or older (or 65 and older among blacks and Hispanics in the U.S.). The trial cohort was a median age 74 years at the time of enrollment in 2010-2014; 56.4% were women and 91.3% were white. The lack of racial diversity limits the generalizability of the trial, the authors said.
For more information: https://www.medpagetoday.com/cardiology/prevention/75123
COPD World News - Week of September 9, 2018
Flu Vax Rates Rise with EHR Nudge
Philadelphia, PA - Primary care clinics who implemented an "active choice intervention" into their electronic health record (EHR) systems were associated with a significant increase in influenza vaccination rates, researchers found. Though vaccination rates declined as the day progressed, adjusted analyses showed that practices that implemented the intervention had a 9.5 percentage point increase in vaccination rates compared with previous practices over time, reported Mitesh S. Patel, MD, of the University of Pennsylvania in Philadelphia, and colleagues, writing in JAMA Network Open. They noted that "'nudges' can have outsized effects on medical decision making," but that while a prior study found an order to accept or decline influenza vaccinations in the EHR increased vaccination rates, it "could lead to clinician alert fatigue." Prior to expanding the practice, the authors then redirected the alerts to medical assistants, who could ask patients about influenza vaccination and "template orders in the EHR for clinicians to review." The researchers examined data from 11 primary care practices in the University of Pennsylvania Health System for the 2014-2015, 2015-2016, and 2016-2017 influenza seasons. Three of these practices were intervention practices, while eight were control practices. The intervention was comprised of medical assistants being prompted to order the influenza vaccine in the EHR, and the clinician could accept or decline the order. The authors noted that "prior to the intervention, [primary care practitioners] had to remember to manually check if a patient was due for an influenza vaccination, discuss it with the patient, and then place an order for it in the EHR." Overall, the sample included about 96,000 patients, who were a mean age of 56; about 44% were men, and almost two-thirds were white. Unadjusted vaccination rates ranged from 44% with appointments from 8 am to 10 am to 32.0% at 4 pm. The authors found that compared with the 8 am appointment time, adjusted odds ratios of vaccination were "significantly lower for each subsequent hour of the day and for the overall linear trend". In addition, "adjusted preintervention trends during the first 2 years did not differ between groups
For more information: https://www.medpagetoday.com/primarycare/uritheflu/75121
COPD World News - Week of September 2, 2018
Flu vaccine may be more effective in females than males
Vancouver, BC - Data from seven recent influenza seasons in Canada showed the influenza vaccine may be more effective in females than males, according to study findings published in Open Forum Infectious Diseases. Between 2010-2011 and 2016-2017, overall vaccine effectiveness was 49% for females and 38% for males, according to Danuta Skowronski, MD, MHSc, FRCPC, physician epidemiologist at the BC Centre for Disease Control and clinical professor in the school of population and public health at the University of British Columbia, and colleagues. “As with other medical interventions, it has previously been assumed that males and females respond the same way to vaccination, but our findings question the validity of that assumption for influenza vaccine,” Skowronski told Infectious Disease News. “The effect of sex on influenza vaccine protection that we observed was not large, and our findings cannot be considered conclusive. They are best interpreted as a prompt for more definitive investigation of possible sex effects on influenza vaccine protection.” According to the researchers, influenza vaccination coverage rates are higher among young adult women than young men in the United States and Canada. Additionally, they noted that many women work in health care and tend to be the primary caregiver for children and the elderly, increasing their likelihood of influenza exposure. Skowronski and colleagues investigated sex as a potential variable for the effectiveness of the influenza vaccine. They analyzed influenza vaccine effectiveness data from 2010-2011 to 2016-2017 from Canadian Sentinel Practitioner Surveillance Network (SPSN) databases. Sentinel practitioners collected respiratory samples from patients aged 1 year or older who presented within 7 days of influenza-like illness onset. Patients who tested positive for influenza by RT-PCR were included in the study, and patients who tested negative were added to the control group. Vaccination status, which was largely self-reported, was dependent upon patients receiving the seasonal influenza vaccine at least 2 weeks before symptom onset. According to the study, 60% of the SPSN participants were female and 40% were male. This trend was observed among influenza cases and test-negative controls, Skowronski and colleagues said. However, 40% of females tested positive for influenza compared with 43% of males (P <.01). The higher vaccination coverageamong females may account for why females were slightly less likely to test positive for influenza. Overall, 29% of females and 23% of males were vaccinated (P <.01). Similarly, 34% of female and 27% of male controls were vaccinated (P <.01). Adjusted vaccination effectiveness varied by influenza subtype/lineage, age group and season, although effectiveness was higher among females compared with males, 49% (95% CI, 43%-55%) vs. 38% (95% CI, 28%-46% [absolute difference (AD) = 11%, P =.03]). Age was also considered in the analysis, and the researchers observed the greatest difference in vaccine effectiveness between men and women among adults aged 50 years and older. In this group, adjusted vaccine effectiveness was 48% for women (95% CI, 38%-57%) compared with 29% for men (95% CI, 10%-44% [AD = 19%, P =.03]). In participants younger than age 20 years, vaccination effectiveness was closer between the sexes: 49% among females (95% CI, 31%-62%) and 45% among males (95% CI, 24%-59% [AD = 4%, P=.74]). According to the study, the majority of SPSN participants were aged 20 to 49 years and vaccination effectiveness was slightly higher in men (48%; 95% CI, 33%-60%) than in women (47%; 95% CI, 37%-56% [AD = -1%, P =.90]). Skowronski called the clinical implications of the findings “uncertain.” The researchers emphasized that more definitive research into the association between sex, age and vaccination effectiveness is needed. “Ideally, sex differences would be explored through gold standard randomized controlled trial (RCT) design,” Skowronski said. “To begin, pre-existing RCT datasets could also be retrospectively explored for sex differences in influenza vaccine efficacy and if the signal we report is confirmed, future studies might include the collection of biological specimens to investigate potential underlying mechanisms (hormonal, immunological, genetic).”
For more information: https://tinyurl.com/yd2ks75w
COPD World News - Week of August 26, 2018
Declining lung function associated with heart failure risk
Boston, MA - Rapid decline in lung function, measured by serial spirometry, was associated with a greater incidence of heart failure and other cardiovascular disease outcomes, according to new research. Specifically, a rapid drop in forced expiratory volume in 1 second (FEV1) was associated with a fourfold increased risk of incident heart failure during the first year of follow-up in a community-based cohort of more than 10,000 participants enrolled in the prospective Atherosclerosis Risk in Communities (ARIC) study. Rapid decline in lung function measured by forced vital capacity (FVC) was associated with elevated heart failure risk throughout approximately 17 years of follow-up in the study online in the Journal of the American College of Cardiology. "Neither sex nor race significantly modified these associations," wrote Amil Shah, MD, of Brigham and Women's Hospital in Boston, and colleagues. "These findings demonstrate that deterioration in lung function is a predictor of incident cardiovascular disease, independent of smoking status and baseline lung function." The researchers noted that while rapid lung function decline is a well-known predictor of incident chronic obstructive pulmonary disease and coronary disease mortality, the association with incident cardiovascular events is not well understood. "Incipient or early heart failure may cause rapid deterioration in spirometric measures, and FEV1 in particular, due to interstitial and alveolar edema and consequent airway compression. However, rapid lung function decline secondary to early and undiagnosed heart failure (reserve causality) would be expected to predict incident heart failure during short-term as opposed to long term follow-up," the team wrote. Shah and co-authors hypothesized that declines in pulmonary function would be associated with an increase in risk for heart failure, stroke, coronary disease, and death over 2 decades of follow-up in a cohort of middle-aged individuals free of cardiovascular disease at baseline. The analysis included 10,351 participants in the ARIC study who were free of prevalent cardiovascular disease.
For more information: https://tinyurl.com/y74ghcc7
COPD World News - Week of August 19, 2018
Considerations for the correct diagnosis of COPD
San Antonio, TX - This review highlights the differences in diagnosis and treatment between COPD, asthma, and ACO and discusses the data supporting guideline recommendations for use of bronchodilators in COPD treatment in contrast to asthma or ACO. Despite the availability of well-established recommendations for diagnosis and management, COPD is often misdiagnosed and inappropriately treated in many patients, with approximately 50% of adults with COPD in the United States misdiagnosed or undiagnosed. Despite a common pathophysiology, COPD is a distinct disease from adult-onset asthma and clinicians need to be confident in their diagnosis to ensure the correct treatment. To further complicate the matter, approximately 15% to 20% of patients with COPD may present with features of asthma, described as asthma-COPD overlap (ACO). Long-acting β2-agonist (LABA) bronchodilators and inhaled corticosteroids (ICS) both have a place in standard maintenance treatment of COPD and asthma; however, recommendations for use differ widely between diagnoses. In patients with COPD, LABAs are effective initial monotherapy treatments, whereas ICS use is only recommended in combination with LABA treatment in patients with more advanced disease. Contrastingly, ICS monotherapy is recommended as initial treatment in patients with asthma, whereas LABA monotherapy was associated with an increase in asthma-related death, resulting in a “black box” warning being required on LABA-containing drug labels. It is recommended that LABAs always be administered in combination with ICS when treating persistent asthma of any severity. There is limited pharmacologic evidence for the optimal treatment of ACO because these patients have historically been excluded from clinical trials. However, it is recommended that patients with ACO not be treated with a LABA without an ICS. A diagnosis of COPD should be considered in patients who have symptoms such as dyspnea, chronic cough or sputum production, and/or a history of exposure to risk factors such as tobacco smoke or occupational exposures. Importantly, postbronchodilator spirometry is required to confirm the presence of persistent airflow limitation. In some patients with mild airflow obstruction, spirometry values may be normalized with smoking cessation or use of bronchodilators. In fact, up to 27.2% of subjects in a Canadian study and 15.6% of smokers in a Spanish study had a reversal of their COPD diagnosis. Therefore, patients initially diagnosed with COPD, even those admitted with an exacerbation, should be reassessed at follow-up to avoid overdiagnosis and overtreatment.
For more information: https://journal.chestnet.org/article/S0012-3692(18)30390-8/fulltext
COPD World News - Week of August 12, 2018
Study looks at women with asthma going on to develop COPD
Toronto, ON - Researchers here have found that over 40% of women with asthma could go on to develop chronic obstructive pulmonary disease (COPD). Scientists looked at the long-term health records of 4,051 women with asthma living in Ontario, Canada. They found that 1,701 – or 42% – of the women went on to develop COPD. When a person has symptoms of both asthma and COPD, their condition is often referred to as asthma and COPD overlap syndrome (ACOS). People that have ACOS are more likely to have more flare-ups of their symptoms and to need more hospital treatment, and tend to feel more unwell than people that have just asthma or COPD. The researchers wanted to understand more about why some of the women with asthma developed ACOS, and why others did not. Using their health records, they compared a number of lifestyle and environmental risk factors among these women to see if there were any trends. They found that women who were heavy smokers were at a higher risk of going on to develop ACOS – though 38% of those who did had never smoked. Other factors associated with a higher risk of ACOS included being obese, living in rural areas, having lower education levels and being unemployed. The researchers therefore recommend that people with asthma are given support to live as healthily as possible – such as help with quitting smoking, eating healthily and being physically active. The study was supported by the Ontario Thoracic Society and was published in the Annals of the American Thoracic Society.
For more information: https://tinyurl.com/ycewvcsa
COPD World News - Week of August 5, 2018
Annual lung cancer screening recommended in high-risk adults 55-74
Ottawa, ON - The Canadian Task Force on Preventive Health Care now recommends screening using low-dose CT scans in high-risk adults aged 55-74 years who are current or former smokers with a smoking history of at least 30 pack-years, defined as the average number of packs smoked daily multiplied by the number of years of smoking. This is a big step in the fight against lung cancer, which is the leading cause of cancer related death in Canada. The earlier lung cancer is diagnosed, the better the opportunity for curative treatment. Much of the great improvement that has been seen in survival in cancers such as breast, colorectal and cervical have been due to finding the cancers earlier through regular testing, even of those at just moderate risk, such as from age. However, almost half (48%) of lung cancer diagnoses are made only when the cancer is already at stage 4, the most advanced stage, meaning it has already spread outside of the lung, and a further 27% of cases are diagnosed only at stage 3. The newest screening method, low-dose computed tomography (LDCT) screening, offers much greater promise by yielding a more comprehensive view of the lung tissue while exposing patients to only 20% of the normal CT scan radiation. An expert panel convened by the Canadian Partnership Against Cancer in 2011 to review lung cancer screening reported that a comprehensive program of LDCT screening in Canadians at risk for lung cancer could be expected to save more than 1,200 lives per year, based on results of the National Lung Screening Trial in the US. In Canada, the Pan-Canadian Early Detection of Lung Cancer Study examined both how to incorporate lung cancer screening into our health care systems, and how much it would cost. This study found that screening has the potential to save the health care system a significant amount of money. In this study, the average cost to screen individuals at high risk for developing lung cancer using LDCT was $453 for the initial 18 months of screening following a baseline scan. If a patient can be treated using curative surgery, the average cost was $33,344 over two years. This is significantly lower than the average per person cost of $47,792 used in treating advanced-stage lung cancer with chemotherapy, radiotherapy or supportive care alone. The recommendation for lung cancer screening is a significant one. To date, no province has adopted a comprehensive lung cancer screening program. Lung Cancer Canada believes that lung cancer screening can save lives and lessen the significant burden on the healthcare system and have called on all provinces and territories to adopt screening programs that, at the very least, target patients with the highest risk of lung cancer.
For more information: http://www.lungcancercanada.ca/Lung-Cancer/Screening.aspx
COPD World News - Week of July 29, 2018
Aspirin use and progression of emphysema-like characteristics on CT imaging
New York, NY - Researchers here hypothesized that regular use of aspirin, a platelet inhibitor, would be associated with a slower progression of emphysema-like lung characteristics on CT imaging and a slower decline in lung function. It was noted in their study that platelet activation reduces pulmonary microvascular blood flow and contributes to inflammation; these factors have been implicated in the pathogenesis of COPD and emphysema. The Multi-Ethnic Study of Atherosclerosis (MESA) enrolled participants 45 to 84 years of age without clinical cardiovascular disease from 2000 to 2002. The MESA Lung Study assessed the percentage of emphysema-like lung below –950 Hounsfield units (“percent emphysema”) on cardiac (2000-2007) and full-lung CT scans (2010-2012). Regular aspirin use was defined as 3 or more days per week. Mixed-effect models adjusted for demographics, anthropometric features, smoking, hypertension, angiotensin-converting enzyme inhibitor or angiotensin II-receptor blocker use, C-reactive protein levels, sphingomyelin levels, and scanner factors. At baseline, the 4,257 participants' mean (± SD) age was 61 ± 10 years, 54% were ever smokers, and 22% used aspirin regularly. On average, percent emphysema increased 0.60 percentage points over 10 years (95% CI, 0.35-0.94). Progression of percent emphysema was slower among regular aspirin users compared with patients who did not use aspirin (fully adjusted model: –0.34% /10 years, 95% CI, –0.60 to –0.08; P = .01). Results were similar in ever smokers and with doses of 81 and 300 to 325 mg and were of greater magnitude among those with airflow limitation. No association was found between aspirin use and change in lung function. The researchers concluded that regular aspirin use was associated with a more than 50% reduction in the rate of emphysema progression over 10 years. They added that further study of aspirin and platelets in emphysema may be warranted. Lead author of the study is Carrie P. Aaron, MD., Assistant Professor of Medicine at Columbia University Medical Center, New York Presbyterian Hospital
For more information: https://journal.chestnet.org/article/S0012-3692(17)33210-5/fulltext
COPD World News - Week of July 22, 2018
Smoking rates projected to drop below 10% in 20 years
Toronto, ON – In 2003, tobacco smoking accounted for 9.5 per cent of all health spending in Ontario. By 2041, if the decrease in tobacco smoking rates continues, the researchers say this proportion will drop by more than one-third, to 5.9 per cent of total health spending. Between 2003 and 2041, there will be an estimated $51-billion reduction in tobacco smoking-attributable health care expenditures in Ontario. Despite this reduction, tobacco smoking-attributable health care expenditures will amount to $164 billion between 2003 and 2041. “Tobacco smoking profoundly affects not only health but also almost all aspects of health care. Smoking harms nearly every organ and system in the body. Diseases directly related to smoking are a major source of hospital admission, but even seemingly unrelated admissions are also affected. A person who smokes and has hip surgery will have a greater risk of complications, slower recovery and more likely to require the surgery be redone than a non-smoker,” added Dr. Manuel. The researchers add that investing in strategies to encourage the decrease of unhealthy behaviours such as smoking, ideally preventing the behaviours from starting in the first place, will go far to improve the health of Ontario’s population, while improving the sustainability of our health care system. "Health Care Cost of Smoking in Ontario, 2003 to 2041” is being published July 12, 2018. Author block: Douglas G. Manuel, Andrew S. Wilton, Adrian Rohit Dass, Audrey Laporte, Sima Gandhi and Carol Bennett. The Institute for Clinical Evaluative Sciences (ICES) is an independent, non-profit organization that uses population-based health information to produce knowledge on a broad range of health care issues.
For more information: https://tinyurl.com/ydzanbgo
COPD World News - Week of July 15, 2018
Antidepressants can raise health risks for people with COPD
Toronto, ON - Advocates say this information should be widely disseminated in the medical community, and alternative treatments for COPD patients should be considered. People with chronic pulmonary obstructive disease (COPD) suffer from symptoms that include breathlessness, coughing, and chest tightness. The disease is also associated with mood disorders such as depression and anxiety. By one estimate, as many as 70 percent of COPD patients deal with anxiety and other mood disorders. Now, a new study suggests certain antidepressants may increase the risk of death in people with COPD by 20 percent. Users of serotonergic antidepressants also had higher rates of hospitalization and emergency room visits. Dr. Nicholas Vozoris, lead author of the study and an assistant professor in the Department of Medicine at the University of Toronto, as well as a respirologist at St. Michael’s Hospital, says the findings are not surprising. “These drugs can cause sleepiness, vomiting, and can negatively impact immune system cells. This increases the likelihood of infections, breathing issues, and other respiratory adverse events, especially in patients with COPD,” Vozoris said in an article on the St. Michael’s website. Russell Winwood, an athlete and COPD advocate, argues that the research should be widely disseminated to all physicians, especially those treating respiratory patients. “Unfortunately, information like this can take years to get out into clinics. By this time, many patients can already have experienced adverse side effects,” he said. For John Linnell, another COPD advocate, the new study poses more questions than answers. “I’m very curious if this problem is common knowledge among pulmonologists,” he said. “If it’s common knowledge to every doctor that it’s bad for respiratory patients, then the study is worthless. Well, I shouldn’t say worthless, but it doesn’t mean as much. But if this is something that’s new, that pulmonologists are not aware of, and it’s the primary care physician doing the prescribing and the pulmonologist is unaware of it, and all of a sudden, you’ve got more re-admissions, then yeah, then you’re really onto something.” Linnell agrees that this question is a major issue. “Who is prescribing the antidepressant? Is it the pulmonologist? Or is it the primary care physician?” he asked. Linnell added he knows from personal experience the problematic nature of several doctors managing one patient. “None of them knew what the other was doing at all unless I took the burden upon myself to let them know,” he said. “The underlying message is that the patient needs to make sure that one doctor needs to know what the other doctor is doing.” For COPD advocates, it’s clear there’s an association with COPD and mood disorders. Linnell, among others, suggests anxiety and depression are due to the nature of the disease. “A lot of times because, well, you become anxious because you can’t breathe,” he explained. He added that depression occurs because COPD patients spend so much time at home. “They don’t get out, which makes their COPD worse,” he said. Winwood expressed similar sentiments, stating that COPD is an isolating disease with a lot of stigma still attached to it. “COPD is misunderstood by many people,” he said.
For more information: https://tinyurl.com/ydbegpgk
For more information: https://tinyurl.com/ydbegpgk
COPD World News - Week of July 8, 2018
Pot smokers have more respiratory symptoms
San Francisco, CA - Frequent marijuana use was associated with an increase in respiratory symptoms, including cough, sputum production and wheezing, in a newly published meta-analysis, but the quality of the evidence was poor, researchers reported. They concluded that there was low-strength evidence linking marijuana smoking with the respiratory symptoms in the more than 20 studies included in the analysis and insufficient evidence to link daily marijuana use to changes in pulmonary function or development of obstructive lung disease. "Given rapidly expanding use, we need large-scale longitudinal studies examining the long-term pulmonary effects of daily marijuana use," wrote Mehrnaz Ghasemiesfe, MD, and colleagues, wrote in Annals of Internal Medicine. Ghasemiesfe explained that several previous prospective studies have linked marijuana use with an increased risk for respiratory issues, but evidence of an effect on pulmonary function and obstructive lung disease has been limited by use of marijuana in primarily younger populations. He said the study highlights the limitations of previous research examining marijuana use and pulmonary outcomes, including the lack of standardized use assessment tools and well-defined study designs with robust assessment and adequate follow-up. "Future studies need to focus on middle-aged to older populations who have been heavier marijuana users to identify the potential effects on lung function and developing obstructive lung disease," he said. Ghasemiesfe noted that smoke from burning marijuana contains many of the same toxic gases, particulates and polycyclic aromatic hydrocarbons as cigarette smoke. Ghasemiesfe and colleagues conducted data searches of studies conducted between 1973 and 2018, identifying 22 studies that met their inclusion criteria, including 10 prospective cohort studies and 12 cross-sectional studies. Methods of quantifying marijuana use varied (i.e., as monthly, weekly, or daily). The researchers used the "joint-year" -- the equivalent of one marijuana cigarette a day for 1 year -- as their measure of lifetime exposure. Across all outcomes and studies, 1,255 participants had more than 10 joint-years of exposure and 756 marijuana-only smokers had more than 20 joint-years. Four prospective observational studies and seven cross-sectional studies examined the association between marijuana use and cough, sputum production, wheezing, or dyspnea. One prospective study with moderate risk of bias (ROB) followed a random sample of the population of Tucson, Arizona (n = 1,802), in four sequential surveys from 1981 through 1988, finding current marijuana smoking to be associated with the following: Chronic cough, chronic sputum production, and wheezing. The researchers noted that while the study had strengths (robust exposure assessment and moderate length of follow-up), it presented limited data and could not be included in the pooled analysis. Another prospective study with moderate ROB included participants from Los Angeles, California (n=299), who had smoked a mean of 3.0 (SE 0.4) joints per day for 9.8 years. Baseline exposure assessment was adequate, but half the participants were lost to follow-up. Two prospective studies (low ROB) used the Dunedin Multidisciplinary Health and Development cohort of 1,037 children born in New Zealand between 1972 and 1973. Marijuana exposure data were collected several times during 15 years of follow-up. Compared to non-smokers, marijuana users had increased risks for cough (RR 2.04, 95% CI 1.02 to 4.06) and sputum production (RR 3.84, 95% CI 1.62 to 9.07). The studies found that quitting smoking marijuana led to a significant reduction in respiratory symptoms. No relationship was found between marijuana use and impairment of spirometric indices, but the researchers warned that this finding should be interpreted with caution, noting that exposures may have been insufficient to alter pulmonary function test results. "Because obstructive lung disease develops in only about a third of long-term tobacco smokers, is usually not identified until after age 35 or 40 years, and increases in prevalence with age, large cohorts with middle-aged to older populations of heavier marijuana users may be necessary to identify effects on lung function and obstructive lung disease," the researchers wrote. "On the other hand, given the psychoactive effects of tetrahydrocannabinol and its effect on overall function, few users may have heavy enough exposure to cause significant changes in pulmonary function testing. In other words, marijuana's effect on lung function may not be among its most important health outcomes in the long term."
For more information: https://tinyurl.com/y7f8d28u
For more information: https://tinyurl.com/y7f8d28u
COPD World News - Week of July 1, 2018
Small airways disease in mild and moderate COPD
Vancouver, BC - The concept that small conducting airways less than 2 mm in diameter become the major site of airflow obstruction in chronic obstructive pulmonary disease (COPD) is well established in the scientific literature, and the last generation of small conducting airways, terminal bronchioles, are known to be destroyed in patients with very severe COPD. Researchers here aimed to determine whether destruction of the terminal and transitional bronchioles (the first generation of respiratory airways) occurs before, or in parallel with, emphysematous tissue destruction. In this cross-sectional analysis, they applied a novel multiresolution CT imaging protocol to tissue samples obtained using a systematic uniform sampling method to obtain representative unbiased samples of the whole lung or lobe of smokers with normal lung function (controls) and patients with mild COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 1), moderate COPD (GOLD 2), or very severe COPD (GOLD 4). Patients with GOLD 1 or GOLD 2 COPD and smokers with normal lung function had undergone lobectomy and pneumonectomy, and patients with GOLD 4 COPD had undergone lung transplantation. Lung tissue samples were used for stereological assessment of the number and morphology of terminal and transitional bronchioles, airspace size (mean linear intercept), and alveolar surface area. Of the 34 patients included in this study, ten were controls (smokers with normal lung function), ten patients had GOLD 1 COPD, eight had GOLD 2 COPD, and six had GOLD 4 COPD with centrilobular emphysema. The 34 lung specimens provided 262 lung samples. Compared with control smokers, the number of terminal bronchioles decreased by 40% in patients with GOLD 1 COPD (p=0·014) and 43% in patients with GOLD 2 COPD (p=0·036), the number of transitional bronchioles decreased by 56% in patients with GOLD 1 COPD (p=0·0001) and 59% in patients with GOLD 2 COPD (p=0·0001), and alveolar surface area decreased by 33% in patients with GOLD 1 COPD (p=0·019) and 45% in patients with GOLD 2 COPD (p=0·0021). These pathological changes were found to correlate with lung function decline. We also showed significant loss of terminal and transitional bronchioles in lung samples from patients with GOLD 1 or GOLD 2 COPD that had a normal alveolar surface area. Remaining small airways were found to have thickened walls and narrowed lumens, which become more obstructed with increasing COPD GOLD stage. These data show that small airways disease is a pathological feature in mild and moderate COPD. Importantly, this study emphasises that early intervention for disease modification might be required by patients with mild or moderate COPD.For more information: https://tinyurl.com/yaw3vm6b