Caitlyn Bahrenburg

A new study evidences a significant association between current smoking habits and 

chronic obstructive pulmonary disease (COPD)

In a recent analysis designed to determine the relationship between haptoglobin phenotypes and the frequent exacerbator status, compared to COPD non-exacerbators, a team of Israel-based investigators found that the exacerbator phenotype is inversely association with smoking rather than the haptoglobin—a protein produced predominately by the liver&mdash;phenotype.

It has been long established that smoking is significantly correlated with COPD. The 

 currently estimates that 85 to 90% of all COPD cases are caused by cigarette smoking. Though the main cause of COPD is generally smoking, nonsmokers are also susceptible, according to the association.

“When a cigarette burns, it creates more than 7,000 chemicals, many of which are harmful,” the ALA noted. “The toxins in cigarette smoke weaken your lungs' defense against infections, narrow air passages, cause swelling in air tubes and destroy air sacs—all contributing factors for COPD.”

Investigators, from the Pulmonology Institute at Carmel Medical Center in Haifa, observed that frequent COPD exacerbators are at an increased risk of “adverse health outcomes when compared to infrequent exacerbators.”

“Haptoglobin (Hp) polymorphism has been associated with differing clinical outcomes in cardiovascular and renal disease,” investigators wrote.

In humans, 2 types of genes for Hp exist: Hp1 and Hp2, with potential combinations of the genes, according to a 

 The Hp2 phenotype has been found to have bacteriostatic properties, investigators noted, while the Hp1 phenotype is more associated with infections.

Inclusion criteria for the study included patients with a previous COPD diagnosis, as well as the presence of at least 2 documented COPD exacerbations in the previous year, or absence of such exacerbations in the previous 2 years.

Investigators analyzed the data utilizing Fisher’s exact test and the nonparametric Kruskal-Wallis test, in addition to performing a multivariate logistic regression analysis.   

Ultimately, the researchers determined that no relationship existed between haptoglobin polymorphism and frequent exacerbator status.

“Despite its importance, haptoglobin may not be an important contributor to airway uptake of hemoglobin and iron, which may explain the lack of effect of haptoglobin phenotype in these two studies,” the team wrote.

Conversely, the frequent exacerbator status had a statistically significant association with COPD Assessment Test scores and pack-years, as well as a negative correlation with current smoking status.

Smoking status was found to be negatively related with the frequent exacerbator status, with an odds ratio of 0.240. Number of pack-years was negatively related to being a frequent exacerbator, according to the study.

“The impact of smoking status and number of cigarettes smoked on frequent exacerbator status supports the hypothesis that certain people are susceptible to exacerbations due to factors irrespective of smoking history,” investigators wrote. “Our analysis, paradoxically, found that those who continued to smoke at the time of the study were less likely to be frequent exacerbators.”

The team concluded that more studies assessing the observed positive correlation between current smoking and patients being a non-exacerbator should be explored. Such studies, which should also consider the findings that haptoglobin phenotype is not associated with exacerbation status, should include larger patient populations.

COPD Exacerbator Phenotype is Inversely Associated with Current Smoking But Not with Haptoglobin Phenotype

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Researchers determined that no relationship existed between haptoglobin polymorphism and frequent exacerbator status, though a negative one existed between exacerbator status and current smoking habits.

Smoking Associated with Negative COPD Exacerbator Relationship

In the hopes of outlining a pathway that contributes to 

, a new study examined a novel pathogenic entity to determine its impact on chronic inflammation and tissue destruction.

Study coauthor Derek W. Russell, MD, an assistant professor in the Division of Pulmonary, Allergy, and Critical Care Medicine at the University of Alabama at Birmingham School of Medicine, noted in an interview with 

that COPD’s unusual nature comes from the body reacting constantly to harmful inhalants.

“In the US, this usually includes a constant exposure of cigarette smoke, but it can be other irritants [or] pollutants,” Russell said. “The ‘innate’ immune system, cells that are always in our body waiting for bad things to kill, gets overheated and starts to damage the tissues, and in COPD this leads to the spongy lung tissue to die and dissolve, which leaves the lung scarred, floppy, and makes it harder and harder to breathe.”

In cases of COPD, much of the damage appears to be from the innate system, he explained. The body’s own defenses, including proteins that block the dangerous neutrophils’ proteins, can often prevent any harm that results in permanent damage.

Russell and colleagues examined to learn if neutrophil elastase (NE) exists in an exosomal form, and whether these exosomes could potentially bypass alpha1-antitrypsin (A1AT) inhibition to contribute to COPD.

The findings revealed “an unappreciated role for exosomes in the pathogenesis of disorders of extracellular matrix (ECM) homeostasis such as COPD and bronchopulmonary dysplasia (BPD), providing a critical mechanism for proteolytic damage,” authors wrote.

The results of the study concluded that exosomes from activated polymorphonuclear leukocytes (PMN) caused COPD damage when the subcellular particles collected from purified PMNs were injected into the lungs of healthy mice, while exosomes from inactive PMNs did not cause COPD when transferred.

“In the lungs of COPD patients, neutrophils get stimulated by their disease, make NE and it gets coated on the exosomes they are spewing out,” Russell said. “The exosomes with NE on them are much more damaging to lung tissue than the NE that just gets cast to the wind.”

This may be due to the exosomes protecting NE from being blocked by A1AT, as well as because exosomes are able to bind to connective tissue that hold the lung together, he explained. The exosomes are among the major explanations for the “confusing findings” that NE and related enzymes contribute to COPD lung destruction, despite patients’ retained A1AT protective barriers.

The findings of this study have the potential to lead to therapeutic strategies and improved disease monitoring in COPD. Russell added that it seems very likely a similar pathway contributing to other diseases.

“There are many diseases—metastatic cancer, for example&mdash;in which the body's own tissues are damaged by enzymes from the body's own cells, but this is not well-understood yet,” Russell said. “We also do not yet know why the neutrophils make these particles.”

He theorized the particles are meant to “seek and destroy” bacteria or tissue, allowing the neutrophils to access an infected part of the body. But any conclusion would require clinical follow-up.

“We are eager for others to build on this research and unravel the effects these tiny particles have in health and disease,” Russell said.

Activated PMN Exosomes: Pathogenic Entities Causing Matrix Destruction and Disease in the Lung

,” was published online in the journal 

UAB investigators sought to learn if neutrophil elastase exists in an exosomal form, and whether these exosomes could potentially bypass alpha1-antitrypsin inhibition to contribute to COPD.

Investigators Assess Novel Pathogenic Entity's Role in COPD

Heart failure and chronic obstructive pulmonary disease (COPD) are among the leading causes of hospital admissions and mortality in older individuals around the world, according to Claire Lawson, PhD, of her own titular Diabetes Research Centre, University of Leicester, Leicester General Hospital, in the United Kingdom.

“When patients suffer both, their risk of admission and death increases even higher. This which is burdensome for patients and health services and very expensive to manage,” Lawson said in an interview with 

A recent study led by Lawson sought to determine whether the highest risk patients with heart failure and COPD could be identified utilizing readily available data, found that among patients with heart failure.

The study, a United Kingdom-based, nested case-control study with risk-set sampling, utilized the Clinical Practice Research Datalink (CPRD) linked to Hospital Episode Statistics between 2002 and 2014. Participants included 50,114 patients aged 40 years and older with a new diagnosis of HF in their family practice clinical record &shy;—the largest population-based study of heart failure, according to Lawson&mdash;and who had at least three years of CPRD-approved clinical data prior to their study entry.

Patients were followed up until their date of transfer out of practice, their index outcome event, or 2014.

“Our findings show that 1 in 7 patients with heart failure in the community also has COPD, which carries a 30% increase in risk of death and hospitalization compared with patients with HF but without COPD,” investigators wrote.

Lawson and her team found that COPD increased the risk of hospital admission and death by more than one-third, according to the study. However, the study found that increased risk was specific to patients receiving the most intense course of COPD medication, including triple inhaler therapy, prescribed oral corticosteroids, or oxygen therapy, according to the study.

“Those prescribed short-acting inhaled β-mimetics or the most intensive medication regimes were at a much higher risk of admission and death,” Lawson said.  “Patients with more severe airflow limitation were at much higher risk of death and admission as were women. 

These severity markers, she noted, can be used to target patients with HF and COPD in order to optimize treatments for both conditions, to prevent admissions and death.

The number of patients with heart failure who were coded with COPD was significantly lower than the researchers anticipated.

“This means that there are likely to be HF patient’s with COPD that are not known and not treated,” Lawson said.

Additionally, half of the patients coded with COPD had a spirometry reading. The lack of spirometry recording, coupled with the large overlap between heart failure and COPD symptoms, signs, and chest radiography, electrocardiography, and spirometry results, indicates that a significant number of patients may be misdiagnosed with COPD, Lawson said.

“These patients might be wrongly prescribed short-acting inhaled β-mimetics, which we found increases risk,  and not prescribed important HF medications used to improve outcomes,” Lawson said.

Ultimately, the team found that optimal care of patients with heart failure and COPD requires accurate diagnosis and assessment.

“Spirometry should be performed more regularly and when HF patients are euvolemic,” Lawson said. “Specialist tests such as body plethysmography should be made available for community patients to aid diagnosis."

Association of Medication Intensity and Stages of Airflow Limitation With the Risk of Hospitalization or Death in Patients With Heart Failure and Chronic Obstructive Pulmonary Disease

About 1 in 7 heart failure patients have COPD, which can lead to a 30% increase in risk of hospitalization and death.

COPD Increases Hospitalization, Death in Heart Failure Patients

 exacerbations can speed up disease progression, a new analysis found it may also negatively influence patient healthcare costs.

In a study intended to seek an effective risk assessment strategy for COPD, lead author Richard Stanford, PharmD, MS, explained the ongoing difficulty in identifying appropriate candidates for cost-saving and exacerbation-reducing disease management programs, despite such therapies and interventions becoming more prevalent.

“Further, an assessment that could be calculated using readily-accessible medical data to measure exacerbation risk was not readily available,” Stanford explained. “As a result, our research team sought to understand if an easy to calculate risk ratio that uses pharmacy dispensing data would be an effective measure to help health plans and institutions identify patients that were at a higher risk for a COPD-related hospitalization.”

Investigators found that use of a COPD treatment ratio (CTR) has been shown to provide a modifiable measure of risk of COPD exacerbation in a large commercial and Medicare population, and remained a strong predictor in circumstances when pharmacy-only data claims were available.

The retrospective observational study was conducted utilizing Humana research datasets. A separate assessment was performed utilizing pharmacy-only models that excluded risk factors sourced from medical claims.

A total of 92,496 patients were identified, of which 96.2% were Medicare members with a median age of 69 years. Throughout the baseline period of the study, 14% of patients had moderate exacerbation, while 11% had severe exacerbation.

“Overall, the CTR performed well in predicting future COPD exacerbations, especially severe exacerbations,” investigators wrote. “ROC analysis suggested that 0.7 was the optimal cut-point for dichotomizing CTR.”

Investigators further found that patients with a CTR ≥ 0.7 had a 7.9% reduced risk of severe exacerbation than other patients. In pharmacy-only models, the disparity was more significant: patients with a CTR ≥ 0.7 were 17% less likely to experience a severe exacerbation than other patients.

Stanford noted this is third independent population and dataset used to test CTR. The incremental increase of 0.1 in the ratio are associated with incremental reductions in COPD-related hospitalization risk.

“Based on these findings, disease management programs that can improve the CTR by 10% should improve overall outcomes of their targeted COPD population,” Stanford said. “Ultimately, the results of the study stands to have significant impacts on the ways in which COPD is treated, as well as the cost of managing COPD.”

Standord called for the development of risk assessment measures, in order to properly identify at-risk patients and prevent future exacerbations. The CTR may fill that role.

“Based on the findings from this study, incorporation of the CTR into COPD disease management programs that are designed to improve adherence and reduce COPD symptoms could ultimately reduce COPD related hospitalization and costs,” Stanford said.

External Validation of a COPD Risk Measure in a Commercial and Medicare Population: The COPD Treatment Ratio

As costs of treating COPD exacerbation continue to burden patients, investigators sought to determine a risk assessment tool that could lead to reduced costs.