HPD 2024: Bronchitis as an Early Feature of PreCOPD, Role of Mucus Plugs in COPD, and New Findings on Their Exacerbations
Exacerbations of chronic obstructive pulmonary disease (COPD) significantly affect disease progression, quality of life, survival, and cardiovascular events. What to do about them and how to address them most effectively? Why should future treatment also focus more on mucus plugs? And why is it important to consider COPD even in healthy smokers? These topics were discussed by Professor Jadwiga Wedzicha from the National Heart and Lung Institute at Imperial College London during a symposium supported by Angelini at this year's XXVIII Hradec Pulmonary Days.
Enormous Global Burden
COPD represents a global issue − over 380 million patients suffer from this disease and 3 million die annually due to it, making it the 3rd leading cause of death. Additionally, there is a massive burden of undiagnosed COPD, especially in low-income countries.
It is a highly heterogeneous pulmonary disease with chronic respiratory symptoms, the main ones being dyspnea, cough, sputum production − and the more sputum, the higher the likelihood of exacerbation. Mucus production is also a very early feature of progressive COPD.
Exacerbations Are Crucial in Any Stage of COPD
The latest definition of COPD exacerbation characterizes it as an event marked by worsening dyspnea, cough, and sputum over up to 14 days, with an inflammatory reaction. Most exacerbations are caused by viral infections. “I must tell you directly that if an exacerbation occurs, do not wait 14 days to treat it. Exacerbations must be treated promptly. The longer you delay treatment, the worse the outcome. That is my main issue with this definition,” commented the speaker.
Factors predictive of frequent exacerbations, according to a study published as early as 1998, include the number of exacerbations in the previous year, daily cough and sputum production, and poor quality of life. Another study, based on a 4-year data analysis, showed that 25% of pulmonary function decline (FEV1) could be attributed to the impact of exacerbations. Thus, they are important in any stage of COPD. Research from 2017 further showed that the decline in pulmonary function is proportionally much larger in milder forms of COPD (GOLD 1). It is now vital to focus much more on patients with milder forms of the disease and milder exacerbations.
Data from primary care databases in the UK indicate that if a patient has had a severe lower respiratory tract infection before their COPD diagnosis, they will have a severe exacerbation after being diagnosed with COPD. This also aligns with mortality data in the following years. Therefore, patients who report exacerbations at this time should be taken seriously, as Professor Wedzicha emphasized: “This is a very important point, and we must indeed go and investigate patients with COPD. We can do it simultaneously with lung cancer screening.”
Cardiological Relations of Exacerbations
Exacerbations are also related to myocardial infarction. While it is a rare situation, it can occur, and the more exacerbations a patient has, the higher the probability of an ischemic event. Additionally, viral infection can accelerate plaque instability, its disruption, and coronary occlusion.
The recently completed BEACON study (British Early COPD Network Cohort) showed that in a cohort of COPD patients with an average one-second forced expiratory volume (FEV1) of 50% of the predicted value, 85% had coronary artery disease (CAD) although they did not exhibit any angina symptoms. Coronary disease is therefore much more common in these patients than previously thought, and we are dealing with massive multimorbidity.
Bronchitis As an Early Feature of PreCOPD
Symptoms and changes on CT can be present even when lung function is relatively normal according to current knowledge. The speaker emphasized that this aspect is quite crucial because we will have to rethink when exactly COPD begins. The key symptoms are cough and mucus production.
An early feature of preCOPD is bronchitis. It appears at a young age (even in smokers aged 36-43), and crucially, it increases the risk of exacerbation. Data from a British cohort born in 1946 show the prevalence of mucus hypersecretion throughout life: the incidence of chronic bronchitis in smokers increases between the ages of 36 and 43. If they stop smoking, it decreases; if they continue to smoke, the probability of bronchitis increases further. In non-smokers, nothing significant happens. Thus, bronchitis begins early in smokers, in relatively young patients. A similar relationship between smoking, or smoking cessation, and the incidence of bronchitis applies to patients aged 43-64 years.
Recent data show that small airway disease already occurs in younger smokers. By the time they receive a diagnosis, they already have significant changes on CT. The BEACON study focused on healthy smokers with normal lung function and found that a significant portion of the 550 subjects aged 30-45 years already had bronchitis or preCOPD.
Recently, more attention has been paid to “mucus plugs,” which the speaker suggests should be considered for future treatment: “I think the future will really focus on patients with mucus plugs and their treatment. The problem is that we cannot do it currently. It is too labor-intensive.” Additionally, a patient can have mucus plugs without bronchial inflammation. Data presented at the last American Thoracic Society (ATS) congress and published in JAMA show that patients with a higher mucus plug score had a higher risk of death. In the future, we may even phenotype COPD based on mucus.
What Can Be Done Early On?
At the early stages of the disease, mucolytics should already be used – they reduce the frequency of exacerbations and can be used across all stages of disease severity. Importantly, they provide not only effective but also safe therapy. For instance, the RESTORE study confirmed that erdosteine can reduce the frequency of all types of exacerbations − mild, moderate, and severe. Significantly, it also shortens the duration of exacerbations – which is crucial, as the longer the exacerbation, the higher the probability that recovery will not occur. Therefore, patients need to be monitored based on this parameter. Additionally, the use of this treatment has been shown to reduce SGRQ (St. George's Respiratory Questionnaire) scores and improve quality of life.
Initial Pharmacotherapy According to GOLD
The current recommendations of the Global Initiative for Chronic Obstructive Lung Disease (GOLD 2023) state that pharmacotherapy of the disease should begin (if there are no exacerbations or with one non-hospitalized exacerbation) with a bronchodilator (GOLD A group), followed by long-acting muscarinic antagonists (LAMA), long-acting beta2-agonists (LABA), or inhaled corticosteroids (ICS) as the disease progresses. Triple combination therapy reduces exacerbations more than its individual components and has also shown a favorable trend in reducing mortality. In a study with two doses of budesonide (160 and 320 mg), the effects were very similar concerning exacerbations, but the higher dose had a better effect on reducing mortality.
In the presence of evidence such as bronchiectasis or mucus or sputum obstruction, azithromycin may be considered. Caution is necessary for patients with prolonged QT intervals. “I administer it in the winter months, usually from September to April; it is effective even in patients with cystic fibrosis and bronchiectasis and can help reduce exacerbations,” added the speaker from her experience.
Eva Srbová
Editorial staff forProLékaře.cz
Source: Wedzicha J. COPD exacerbations and role of mucus. XXVIII Hradec Pulmonary Days, Hradec Králové, 24-26 April 2024.
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