Adjunctive therapy with azithromycin for moderate and severe acute respiratory distress syndrome: a retrospective, propensity score-matching analysis of prospectively collected data at a single center.

Effective pharmacological therapy has not been established for patients with acute respiratory distress syndrome (ARDS). Macrolides are antibiotics with potent immunomodulatory and anti-inflammatory effects that may be beneficial in ARDS treatment. The objective of this study was to determine the adjunctive effect of azithromycin on survival for patients with ARDS. This single-center, retrospective cohort evaluation of hospitalized patients with moderate or severe ARDS was conducted to assess the impact of intravenous azithromycin on clinical outcomes using a propensity score analysis. All data were collected prospectively as part of ongoing research on the utility of high-resolution computed tomography in ARDS. The primary outcome was 90-day mortality, and the secondary analysis assessed the effect of azithromycin on time to successful discontinuation of mechanical ventilation and 28-day mortality. Of 191 eligible patients with severe or moderate ARDS, 62 were treated with azithromycin. The 62 patients treated with azithromycin and 62 not treated with azithromycin were matched and analysed. Azithromycin use was associated with a statistically significant improvement in 90-day survival rate (Hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.27-0.87; P = 0.015) and a shorter time to successful discontinuation of mechanical ventilation (HR, 1.74; 95% CI, 1.07-2.81; P = 0.026). The 28-day mortality rate tended to be higher in the azithromycin cohort than in the non-azithromycin cohort, but this was not statistically significant. Adjunctive intravenous azithromycin therapy was effective in patients with moderate or severe ARDS. Further prospective randomized controlled trials are needed to confirm this result.

The negative effect of initial high-dose methylprednisolone and tapering regimen for acute respiratory distress syndrome: a retrospective propensity matched cohort study.

BACKGROUND: The efficacy of corticosteroid use in acute respiratory distress syndrome (ARDS) remains controversial. Generally, short-term high-dose corticosteroid therapy is considered to be ineffective in ARDS. On the other hand, low-dose, long-term use of corticosteroids has been reported to be effective since they provide continued inhibition of the systemic inflammatory response syndrome (SIRS) that accompanies ARDS. Thus far, no reports have been published on the efficacy of initiating treatment with a high-dose corticosteroid regimen with tapering. METHODS: We conducted a retrospective observational study involving 186 patients treated at a teaching hospital (68% had sepsis, pneumonia, or aspiration pneumonia). ARDS was diagnosed according to the Berlin definition. Patients were divided into a high-dose (n = 21) or low-dose corticosteroid group (n = 165) to compare the effectiveness of a down-titration regimen. The primary medical team chose which treatment a patient would receive. We were careful to conduct a differential diagnosis of interstitial pneumonia (e.g., acute eosinophilic pneumonia) since corticosteroid treatment has been proven effective in that patient population. The primary outcome was the 60-day mortality rate. The secondary outcome was the number of ventilator-free days (VFD). RESULTS: Those started on a high-dose regimen had a significantly higher 60-day mortality rate (P = 0.031) with significantly fewer VFD (P = 0.021). Propensity scores were used to adjust patient backgrounds in a variable analysis that also showed the high-dose regimen was a factor in decreasing VFD (OR, 95.63; 95% CI, 1.74-5271.07; P = 0.026) and worsening the 60-day mortality rate (OR, 2.54; 95% CI, 0.92-7.02; P = 0.072). CONCLUSIONS: A tapering regimen after high-dose corticosteroids is likely to increase ventilator dependency and might aggravate the prognosis of patients with ARDS diagnosed according to the Berlin definition.

Efficacy of azithromycin in sepsis-associated acute respiratory distress syndrome: a retrospective study and propensity score analysis.

PURPOSE: Acute respiratory distress syndrome is a life-threatening form of respiratory failure without an established pharmacological treatment. Recently, macrolides have been found to be beneficial in cases of acute lung injury, but evidence is limited. MATERIALS AND METHODS: This single-centre retrospective cohort evaluation of hospitalized patients with sepsis-associated acute respiratory distress syndrome aimed to assess the impact of azithromycin on clinical outcomes by using a propensity score analysis. All data were collected prospectively as part of ongoing research on high-resolution computed tomography of acute respiratory distress syndrome. The primary outcome was 60-day mortality; the secondary outcome was the number of ventilator-free days. RESULTS: Twenty-nine of 125 patients with sepsis-associated acute respiratory distress syndrome (23.2 %) received azithromycin within 24 h after acute respiratory distress syndrome diagnosis. After adjusting for potentially confounding covariates, azithromycin use was associated with lower 60-day mortality (hazard ratio, 0.31; 95 % confidence interval, 0.11-082; P = 0.02) and a shorter time to successful discontinuation of mechanical ventilation. CONCLUSIONS: Azithromycin use was associated with decreased mortality and ventilator dependency in patients with sepsis-associated acute respiratory distress syndrome. Further well-designed prospective studies are needed.

[Solid malignancy in patients who received cyclosporine for fibrosing interstitial pneumonia].

OBJECTIVE: Since more solid malignancies are observed in transplant recipients treated with cyclosporine (CsA) than in healthy persons. We sought to describe the incidence of malignancy in patients treated with CsA for fibrosing interstitial pneumonia. METHODS: We prospectively reviewed 43 patients who received CsA and prednisolone for fibrosing interstitial pneumonia over 180 days at our hospital between April 2004 and October 2008. The duration of CsA treatment was 632 +/- 364 days. RESULTS: Malignancy developed in 6 (14.0%) patients. Time to diagnosis after medical intervention ranged from 394 days to 1325 days (mean, 783 days). Non-small cell lung cancer was diagnosed in 4 cases. These were discovered by routine computed tomography in all cases. Hepatocellular carcinoma and gastric cancer were each diagnosed in 1 case, respectively. Incidence of malignancy tended to be higher in patients who had been treated with CsA for 567 days or more than in those who had been treated for less than 567 days, but this was not statistically significant. CONCLUSION: Our results highlight the need for close follow-up for patients who receive CsA for over 2 years. This could lead to cancer detection at an early stage.