Breath-Based Diagnosis of Infectious Diseases: A Review of the Current Landscape.

Various analytical methods can be applied to concentrate, separate, and examine trace volatile organic metabolites in the breath, with the potential for noninvasive, rapid, real-time identification of various disease processes, including an array of microbial infections. Although biomarker discovery and validation in microbial infections can be technically challenging, it is an approach that has shown great promise, especially for infections that are particularly difficult to identify with standard culture and molecular amplification-based approaches. This article discusses the current state of breath analysis for the diagnosis of infectious diseases.

Breath-based diagnosis of fungal infections.

Invasive aspergillosis and other invasive fungal infections are associated with significant morbidity and mortality in immunocompromised patients, in large part due to limitations of existing diagnostic methods for these infections. Detection of species-specific volatile sesquiterpene metabolites of fungal origin in the breath of patients with invasive fungal infections allows the diagnosis and monitoring of these infections in vivo, non-invasively and more rapidly than possible with current diagnostic methods. While detection of exogenous microbial volatile metabolites in the breath has opened up a new and exciting dimension of diagnostic research and development in infectious diseases, we discuss the daunting challenges to volatile diagnostic biomarker discovery and clinical development.

Comparison of extracorporeal photopheresis and alemtuzumab for the treatment of chronic lung allograft dysfunction.

BACKGROUND: Survival after lung transplantation is limited by chronic lung allograft dysfunction (CLAD). Immunomodulatory therapies such as extracorporeal photopheresis (ECP) and alemtuzumab (AL) have been described for refractory CLAD, but comparative outcomes are not well defined. METHODS: We retrospectively reviewed spirometric values and clinical outcomes after therapy with ECP, AL, or no treatment (NT) in patients with CLAD who underwent transplant between January 2005 and December 2014. We used inverse probability-weighted regression adjustment (IPWRA) to adjust for potential confounders affecting treatment choice. RESULTS: Of 267 patients, 31 received immunomodulatory therapies for CLAD, and 78 received NT. The slope of forced expiratory volume in 1 second (FEV1) decline significantly improved after treatment with AL and with ECP compared with pre-treatment FEV1 slope; however, there was no significant change in slope of forced vital capacity (FVC). Comparison with NT was limited because of clinical differences in treatment groups. After IPWRA, we found no significant difference in mean difference of FEV1 slope (ml/month) when comparing treatment with NT, suggesting stabilization of lung function in the treatment group. We found no difference between the 2 immunomodulatory therapies 1, 3, and 6 months post-treatment (-49.9 [95% CI -581.8, +482.0], p = 0.85; +27.7 [95% CI -167.6, +223.0], p = 0.78; -9.6 [95% CI -167.5, +148.2], p = 0.91). We found no difference in mean FVC slope or differences between ECP and AL in infection rates or survival after treatment. CONCLUSIONS: Immunomodulatory therapy for CLAD with ECP or AL was associated with a significant change in FEV1 slope post-treatment compared with pre-treatment slope, with minimal effect on FVC. There was no difference between the 2 therapies in their effect on pulmonary function.