Azithromycin Improves Survival in Idiopathic Pulmonary Fibrosis

Azithromycin lowered mortality more than fluoroquinolones in patients with an acute exacerbation of idiopathic pulmonary fibrosis (IPF) according to study results published in BioMed Central Pulmonary Medicine.¹

Kodai Kawamura, MD, PhD, from the division of respiratory medicine, Saiseikai Kumamoto Hospital in Japan and lead study investigator spoke with Pulmonology Advisor on the significance of the research. “Our study shows that azithromycin may be an effective treatment option for those patients experiencing an acute exacerbation of idiopathic pulmonary fibrosis,” said Dr Kawamura.

IPF is a chronic, progressive, and ultimately fatal lung disease.² Currently, the prognosis for acute exacerbations is extremely poor with no effective treatments³ and a reported incidence rate of 14.2% and 20.7% at 1 and 3 years, respectively.⁴

In 2012, a study by Walkey, et al⁵ showed macrolide antibiotics used within 24 hours of an acute lung injury were associated with a lower risk of mortality compared with patients not receiving macrolides. This information, along with the approval of intravenous azithromycin for clinical use in Japan, led the researchers to routinely use azithromycin, which has immunomodulatory and anti-inflammatory effects, for acute respiratory failure, beginning in July 2012.¹

Subsequently, in 2014, the researchers published a study⁶ comparing azithromycin with fluoroquinolones for acute exacerbation of chronic fibrosing interstitial pneumonia, reporting lower mortality at 60 days with azithromycin.

To assess the effectiveness of macrolides on patients with acute exacerbations of IPF, the researchers retrospectively compared 38 adults treated with azithromycin after 2012 to 47 historical controls treated with fluoroquinolones before 2012. IPF was diagnosed by consensus criteria,⁷ with the researchers including patients having features of interstitial pneumonia and traction bronchiectasis. The diagnosis of idiopathic acute exacerbations of IPF was made based on criteria from the International Working Group.⁸

All patients were treated with methylprednisolone pulse therapy (1000 mg/day for 3 days) and tapering (0.5-1.0 mg/kg/day). Azithromycin (500 mg/day) was continued for 5 days.

Results showed the 60-day mortality rate was lower in the azithromycin group than the fluoroquinolone group (26% vs 70%; P <.001). Mortality was invariably due to respiratory failure.

Multivariate analysis revealed the APACHE II score (hazard ratio [HR]: 1.1; 95% confidence interval [CI]: 1.01-1.19; P =.002) and azithromycin use (HR: 0.29; 95% CI: 0.14-0.60; P <.001) were independently correlated with 60-day mortality.

In addition, the inverse probability of treatment weighting with propensity score adjustment confirmed azithromycin was associated with lower mortality (HR: 0.28; 95% CI: 0.13-0.61; P =.001).

Study Limitations

• In addition to the small sample size, the study was retrospective, possibly introducing bias
• The long study period may have led to improvements in supportive care, causing differences in outcomes between groups
• The researchers did not collect baseline pulmonary function data before the acute exacerbations
• Results may not apply to patients with acute exacerbation from infection
• Fluoroquinolones may have a harmful effect on acute exacerbations of IPF

References

1. Kawamura K, Ichikado K, Yasuda Y, Anan K, Suga M. Azithromycin for idiopathic acute exacerbation of idiopathic pulmonary fibrosis: a retrospective single-center study. BMC Pulm Med. 2017;17(1):94. doi:10.1186/s12890-017-0437-z
2. Paterniti MO, Bi Y, Rekić D, Wang Y, Karimi-Shah BA, Chowdhury BA. Acute exacerbation and decline in forced vital capacity are associated with increased mortality in idiopathic pulmonary fibrosis [published online April 7, 2017]. Ann Am Thorac Soc. doi:10.1513/AnnalsATS.201606-458OC
3. Tomioka H, Takada H. Treatment with nintedanib for acute exacerbation of idiopathic pulmonary fibrosis. Respirol Case Rep. 2017;5(2):e00215. doi:10.1002/rcr2.215
4. Song JW, Hong SB, Lim CM, Koh Y, Kim DS. Acute exacerbation of idiopathic pulmonary fibrosis: incidence, risk factors and outcome. Eur Respir J. 2011;37(2):356-363. doi:10.1183/09031936.00159709
5. Walkey AJ, Wiener RS. Macrolide antibiotics and survival in patients with acute lung injury. Chest. 2012;141(5):1153-1159. doi:10.1378/chest.11-1908
6. Kawamura K, Ichikado K, Suga M, Yoshioka M.  Efficacy of azithromycin for treatment of acute exacerbation of chronic fibrosing interstitial pneumonia: a prospective, open-label study with historical controls. Respiration. 2014;87(6):478-484. doi:10.1159/000358443
7. Raghu G, Collard HR, Egan JJ, et al; ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183(6):788-824. doi:10.1164/rccm.2009-040GL
8. Collard HR, Ryerson CJ, Corte TJ, et al. Acute exacerbation of idiopathic pulmonary fibrosis. An International Working Group report. Am J Respir Crit Care Med. 2016;194(3):265-275. doi:10.1164/rccm.201604-0801CI