Oral pentoxifylline as a novel adjunct to standard therapy in pediatric community-acquired pneumonia: a randomized controlled trial

Abstract

BACKGROUND: Pneumonia remains a major cause of childhood illness and death globally, especially in low- and middle-income countries. Despite antibiotic therapy, persistent inflammation and lung injury may delay recovery. This study aimed to evaluate the efficacy of oral pentoxifylline (PTX), combined with standard antibiotic and supportive therapies, for treating hospitalized children with Community-acquired pneumonia (CAP). METHODS: In this randomized controlled trial, 106 children with CAP were randomly assigned to receive either oral pentoxifylline plus standard antibiotic and supportive therapy (n = 53) or standard therapy alone (n = 53), per institutional guidelines. Treatment response was evaluated using predefined clinical criteria (respiratory rate and oxygen saturation), laboratory parameters (hemoglobin, WBC count, CRP, interleukin-6, LDH, D-dimer, serum albumin, and liver enzymes), and lung ultrasound findings, assessed at baseline and after 10 days of treatment. RESULTS: The mean age of enrolled patients was 5.61 ± 3.31 years, and 45.3% were female. After 10 days, the PTX group demonstrated significantly lower respiratory rates (29.17 ± 4.38 vs. 34.02 ± 8.29 breaths/min; p < 0.001) and higher oxygen saturation (97.28 ± 1.32% vs. 96.26 ± 1.55%; p < 0.001) compared with controls. Laboratory improvements in the PTX group included higher hemoglobin and serum albumin and lower WBC count, AST, total bilirubin, CRP, LDH, IL-6, and D-dimer levels (all p < 0.05). Lung ultrasound revealed fewer affected lung zones (3.81 ± 1.75 vs. 5.71 ± 2.14; p < 0.001), greater resolution of confluent B-lines (88.7% vs. 71.7%), and smaller pleural effusions (0.94 ± 0.60 cm vs. 1.65 ± 0.90 cm; p < 0.01). CONCLUSION: Adjunctive oral pentoxifylline improved clinical status, reduced systemic inflammation, and enhanced radiological resolution in children hospitalized with CAP. CLINICAL TRIAL REGISTRATION: At ClinicalTrials.gov (Identifier: NCT06265389). First submitted and met quality control criteria on February 11, 2024; first posted publicly on February 19, 2024. https://clinicaltrials.gov/study/NCT06265389 . IMPACT: Many children with community-acquired pneumonia experience delayed recovery despite effective antibiotic therapy due to persistent inflammation and lung injury. This is the first randomized controlled trial to evaluate the effectiveness of oral pentoxifylline as an adjunct therapy in pediatric pneumonia. Adjunctive oral pentoxifylline improved clinical outcomes, reduced systemic inflammation, and accelerated lung healing.