Even patients with mild chronic obstructive pulmonary disease (COPD) exacerbations can benefit from antibiotics and systemic corticosteroids, according to a systematic review and meta-analysis published online February 24 in the Annals of Internal Medicine.
“The study…lends support to every doctor who prescribes antibiotics and corticosteroids to their patients independently of how severe their exacerbation is,” lead researcher Claudia C. Dobler, MD, PhD, from the Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota, told Medscape Medical News.
“Whether patients have severe disease or more mild disease, they all benefit from getting both steroids and antibiotics,” pulmonologist Wayne Tsuang, MD, MHS, from the Respiratory Institute at Cleveland Clinic, Cleveland, Ohio, told Medscape Medical News.
Clinicians often worry about the side effects of steroids and antibiotics and are reluctant to “overprescribe antibiotics,” continued Tsuang, who was not involved in the study.
However, Dobler and Tsuang note that many of the trials analyzed seemed to miss on outcomes important to patients.
Systemic Antibiotics Increased Odds of Resolution
To better assess the risks and benefits associated with antibiotics and systemic corticosteroids, Dobler and colleagues conducted a systematic review and meta-analysis of pharmacologic interventions for adults experiencing a COPD exacerbation. The studies compared various pharmacologic therapies against placebo, “usual care,” another pharmacologic treatment, “or a different agent type, dosage, application route, or duration of treatment (for antibiotics and systemic corticosteroids only); and reported outcomes of interest,” the authors write.
The researchers included 68 randomized controlled trials involving 10,758 participants published in English through January 2, 2019. The investigators excluded studies with patients who received invasive or noninvasive mechanical ventilation at the start of the intervention.
Patients received treatment in outpatient settings, emergency departments, hospitals, and mixed outpatient and hospital settings. Study interventions ranged in length from 4 to 56 days and follow-up duration ranged from 1 to 12 days.
The researchers looked at seven studies that compared the effectiveness of systemic antibiotics (duration 3 to 14 days) with placebo or management without systemic antibiotics (duration 7 to 10 days) among outpatients (five studies) or inpatients (two studies). Two studies enrolled patients with mild exacerbations, three enrolled those with mild-to-moderate exacerbations, and two enrolled those with moderate-to-severe exacerbations.
Antibiotic treatment was linked to a better likelihood of exacerbation resolution at the end of the intervention (odds ratio [OR], 2.03), with moderate strength of evidence [SOE] and independent of exacerbation severity and study setting.
Studies that examined treatment failure were carried out in outpatients with mild COPD exacerbations. Treatment failure was lower at the end of interventions lasting 7 to 10 days (OR, 0.54; moderate SOE), but not at the longest follow-up conducted at 1 month (OR, 0.82; low SOE).
Antibiotics administered for 7 to 10 days were linked to reductions in dyspnea, cough, and other symptoms in patients with mild-to-moderate and moderate-to-severe exacerbations.
However, there were no significant differences in mortality, quality of life, hospital admissions, repeated exacerbations, intubations, or forced expiratory volume in 1 second (FEV1). Similarly, there was no difference in total number of adverse events, severe adverse events, or study withdrawals resulting from adverse events.
Nine trials compared the effectiveness of systemic corticosteroids administered for 1 to 56 days with placebo or management without systemic corticosteroids. Two trials enrolled patients with mild exacerbations, five enrolled patients with moderate or severe exacerbations, one enrolled those with severe exacerbation, and one enrolled patients with flare-ups ranging from mild to severe.
Systemic corticosteroids were linked to lower treatment failure at the end of the intervention at 9 to 56 days (OR, 0.01; low SOE), independent of exacerbation severity and study setting; however, the number of total and endocrine-related adverse events was higher.
“Systemic corticosteroids were also associated with reduced dyspnea (measured with a numerical scale, low SOE) at the end of the intervention at 7 to 9 days in outpatients with mild (26) and inpatients with moderate to severe (23) exacerbation,” the authors explain.
In all pooled studies and in the studies of patients with mild exacerbation, absolute FEV1 improved at the end of the intervention in those treated with systemic corticosteroids.
Death, admission to hospital, repeated exacerbation, and intubation did not differ significantly.
“We found insufficient or no evidence supporting the use of pharmacologic treatments other than antibiotics and systemic corticosteroids. There was also insufficient or no evidence informing the optimal choice of antibiotic or corticosteroid treatment regimens (agent type, dosage, application route, or duration of treatment),” the authors write.
Improved Lung Function May Not Matter to Patients as Much as Other Outcomes
FEV1 is not really an outcome that’s important to patients, Dobler told Medscape Medical News. “It’s a lung function measurement and it’s not entirely clear how this relates to things that are important to patients, such as how well they can breathe or how good they feel overall and their quality of life,” he said.
“It was quite disappointing when we did this systematic review that a lot of [the studies] have used this outcome and some of them only used this outcome. It’s much better to use outcomes that directly relate to how well patients feel,” Dobler explained.
Tsuang said that patients he sees in the clinic are most concerned about quality of life and the feelings of shortness of breath that they always experience. “We need more research that is patient-centered and patient-focused on the outcomes which they care about.”
Many of the studies examined important health system outcomes such as hospital length of stay and intensive care unit admission, but patients care about shortness of breath and quality of life, Tsuang noted. This suggests the need for nonpharmacologic approaches such as treatment of comorbidities and outpatient physical and pulmonary rehabilitation “as a way to augment or help with the pharmacologic treatment of COPD,” he added.
The findings apply to patients in the community as well as those in the hospital, Dobler emphasized.
Antibiotics combat an infection and the corticosteroids treat the inflammation that occurs in the lungs at the time of an exacerbation, she explained. “We find that this is the case even in patients in the community who don’t need to go to hospital and only maybe have a mild exacerbation.”
The authors and Tsuang have disclosed no relevant financial relationships.
Ann Int Med. Published online February 24, 2020.