BACKGROUND: We hypothesized airway inflammation can be detected non-invasively by induced sputum (IS) or peripheral blood eosinophilia, and IS can detect bacterial and viral infection in preschool children with airway disease, with results comparable to broncho-alveolar lavage (BAL). METHODS: Preschool children with cystic fibrosis, recurrent wheeze, or wet cough underwent IS with nebulized hypertonic saline, chest physiotherapy, and oropharyngeal suction. Samples were analyzed for inflammation by cytology and bacterial culture, viral detection by PCR. Results were compared to BAL and blood in a sub-group undergoing clinically indicated bronchoscopy. RESULTS: 64 children (median age 33 [7-76] months) underwent IS without adverse events. IS was obtained from 61/64. Twenty out of sixty-four underwent BAL and IS, no IS was obtained in 2/23. Thirteen out of twenty-one (62%) had matching bacteria and viruses, 4/21 had positive BAL bacterial growth with negative IS, and 3/21 had negative BAL growth with positive IS. 67% of sputum samples were processed for cytology, 46% had <80% squamous cells; the proportion of squamous cells reduced with increasing age (r = -0.55, P < 0.01). IS was significantly more neutrophilic and less eosinophilic than BAL; 2/21 IS samples contained eosinophils compared to 17/23 BAL. There was a positive correlation between blood and BAL eosinophilia (r = 0.75, P < 0.01). CONCLUSION: IS from preschool children can be used to assess infection. BAL and IS culture concurred in approximately two-thirds. However, inflammation was measureable in only one-third of IS samples and the cell differential was predominantly neutrophilic compared to BAL. Blood eosinophils may provide a better reflection of lower airway eosinophilia in this age group. Pediatr Pulmonol. 2016;51:778-786. © 2015 WileyPeriodicals, Inc.