Impact of the COVID-19 pandemic on COPD exacerbations in Japanese patients: a retrospective study | Scientific … – Nature.com

There was a decrease in COPD exacerbations in the 20202021 fiscal year compared to the 20182019 fiscal year. The difference between the two periods was the COVID-19 pandemic, and the most influential cause was the infection prevention measures including wearing masks. Medical factors other than infection control that may have reduced COPD exacerbations include improved smoking cessation rates associated with increased health motivation, treatment for COPD, and adherence to medications9. We found no significant difference in the rate of smoking cessation. Moreover, the total number of inhaled drugs, such as LAMA/LABA/ICS, which could suggest an intensification of treatment, remained almost the same. There was no apparent change in medication adherence in the medical records, at least for patients who had been continuously monitored in our department before the exacerbation. Additionally, there were reports that air pollutant concentrations have decreased during the lockdown period, associated with economic stagnation, and that the number of hospitalizations for COPD exacerbations and Asthma attacks has also decreased10,11. However, other researchers have reported that medical factors other than infection control have little impact12. Thus, because the main cause of COPD exacerbation is infection, we assumed these environmental effects including social factors remain controversial. Another factor was the reluctance to visit a doctor. There are reports of a temporary decrease in hospital visits due to the belief that hospital visits pose an infection risk following the COVID-19 pandemic13. However, in our hospital, the emergency department is mainly responsible for COVID-19 patients, and the total number of inpatients and outpatients in the respiratory department did not decrease at least, rather had a slight increase due to the expansion of the size of the practice. Additionally, patients who required systemic steroid treatment, such as those with moderate or severe symptoms, were assumed to be less likely to refrain from visiting the doctor. Hence, in this study, we considered that refraining from hospital access would have little effect on the number of COPD exacerbations. Therefore, it can be inferred that the measures taken against COVID-19 reduced the number of respiratory tract infections, which in turn reduced the incidence of COPD exacerbations.

A comparison of the patient population with COPD exacerbations before and during COVID-19 showed that patients who had exacerbations during COVID-19 had significantly lower %FEV1 and BMI. It is known that the milder the progression of COPD airway obstruction, the less frequent the exacerbations; the higher the BMI, the less likely COPD exacerbations occur14,15,16. Infection is the most common cause of the development of COPD exacerbations; however, it is not only influenced by environmental factors, including infection, but also by patient factors, such as frailty, metabolic syndrome, immune, and genetic factors17. Although no precise mechanism has been elucidated, %FEV1 and exacerbations are interrelated. The more exacerbations that occur, the more airway narrowing associated with chronic inflammation progresses. The more lung function declines, more likely exacerbations will occur due to decreased infection defense mechanisms in the patient4,18. The same was true for BMI. Although it is difficult to determine the full distribution of fat/lean body mass throughout the body, more exacerbations occur, and more muscle mass is lost with systemic inflammation. Additionally, more respiratory muscles are reduced, which can lead to more frequent exacerbations19,20.

In addition, the BODE index; B: BMI21; O: Obstruction %FEV165%; D: Dyspnea modified medical research council dyspnea scale1; E: Exercise capacity350m on a 6-min walk, which is widely known as a mortality risk assessment for COPD, can be used as a risk assessment for exacerbations21,22. The significant predictors of COPD exacerbations are low BMI, low pulmonary function, poor health-related quality of life, and a history of previous exacerbations. Moreover, %FEV1 and BMI are clinical parameters that can be obtained in daily practice, are elements with objective criteria, and play a significant role as predictors of COPD exacerbation.

Compared to patients with COPD in Western countries, Japanese patients are older, have a lower BMI (1924 vs. 2628), are more emphysema-dominant (90%), and have fewer comorbidities, such as cardiovascular disease and metabolic syndrome23,24. Nevertheless, Japanese patients have a lower frequency of exacerbations. Moreover, the exacerbation rate of COPD in Japan is low compared to other Asian countries, therefore, rather than racial disparities, universal health insurance system is thought to be the cause25. However, this study, conducted in Japan, also found that few patients had multiple exacerbations. Therefore, daily disease control may also be important in the prevention of COPD exacerbations. Additionally, regarding the possibility of random errors occurring due to sample size, the BMI data was normally distributed, and the 95% confidence interval for the population mean calculated from pre-epidemic data was 21.0923.91, unchanged from previous reports. This was similar to previous reports that exacerbation is more likely to occur with low BMI and low respiratory function which showed a significant difference even with this sample size. Although the possibility of insufficient detection of minute differences cannot be denied, it is assumed that these our result are valid.

In combination with the results of this study, it is possible that infection control measures may have been more effective in preventing exacerbations in patients with relatively infrequent COPD exacerbations, such as those with a maintained %FEV1 or above-standard BMI. We consider that patients with advanced COPD or those who are emaciated and relatively prone to COPD exacerbations might be unable to prevent respiratory infections and exacerbations even with infection control measures, resulting in a relative decline in the mean values of %FEV1 and BMI during the COVID-19 pandemic. These patients may also require further COPD exacerbation prevention that includes more thorough infection preventions and measures for unexplained exacerbations accounting for about one-third which does not rely solely on infection control.

In this study, each 2-year survey period was compared with uniform seasons to evaluate the results throughout the year and to eliminate the effects of the seasonal disparities. We found no significant difference in seasonal variation before and during COVID-19 (Fig.2). During these 4years, there were 1st-6th waves of pandemics, and the incidence in our municipality ranged from 1 to 1508 cases/100,000 persons/month, but there was also no clear correlation with the number of patients with COPD exacerbations.

Number and annual distribution of patients with COPD exacerbations before and during the COVID-19 pandemic. Distribution of the number of exacerbations per month throughout the year. No significant changes are observed in the seasonal distribution of COPD exacerbations before the COVID-19 pandemic; 20182019 fiscal year, and during the COVID-19 pandemic; 20202021 fiscal year.

Nonetheless, a limitation of this study is that it was conducted on patients treated by respiratory medicine specialists at a university hospital and did not include those treated by primary care physicians. However, the fact that most patients underwent spirometry and computed tomography at the time of COPD diagnosis is a strength of this study. Further studies should be conducted in prospective multicenter settings. In addition, because we did not exclude patients with asthma complications, it is possible that we were unable to completely exclude asthma attacks. However, the concept of Asthma and COPD Overlap has become widespread, and even after establishing a diagnosis of COPD in clinical practice, it is difficult to clearly distinguish whether asthma complications are present in many cases. From this point of view, we believe that we were able to conduct a study in line with actual clinical practice while making a more reliable diagnosis of the presence or absence of COPD.

In conclusion, during the COVID-19 pandemic, the number of COPD exacerbations decreased in both inpatient and outpatient settings. The reduction was more substantial in patients with relatively preserved %FEV1 (GOLD IIII) or in less emaciated patients (BMI20). It is suggested that infection control measures may have been effective in preventing exacerbations in COPD patients with relatively preserved BMI and lung function.

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Impact of the COVID-19 pandemic on COPD exacerbations in Japanese patients: a retrospective study | Scientific ... - Nature.com