Personalized Medicine for Chronic Respiratory Infectious Diseases: Tuberculosis, Nontuberculous Mycobacterial Pulmonary Diseases, and Chronic Pulmonary Aspergillosis

Abstract

Chronic respiratory infectious diseases are causing high rates of morbidity and mortality worldwide. Tuberculosis, a major cause of chronic pulmonary infection, is currently responsible for approximately 1.5 million deaths per year. Although important advances in the fight against tuberculosis have been made, the progress towards eradication of this disease is being challenged by the dramatic increase in multidrug-resistant bacilli. Nontuberculous mycobacteria causing pulmonary disease and chronic pulmonary aspergillosis are emerging infectious diseases. In contrast to other infectious diseases, chronic respiratory infections share the trait of having highly variable treatment outcomes despite longstanding antimicrobial therapy. Recent scientific progress indicates that medicine is presently at a transition stage from programmatic to personalized management. We explain current state-of-the-art management concepts of chronic pulmonary infectious diseases as well as the underlying methods for therapeutic decisions and their implications for personalized medicine. Furthermore, we describe promising biomarkers and techniques with the potential to serve future individual treatment concepts in this field of difficult-to-treat patients. These include candidate markers to improve individual risk assessment for disease development, the design of tailor-made drug therapy regimens, and individualized biomarker-guided therapy duration to achieve relapse-free cure. In addition, the use of therapeutic drug monitoring to reach optimal drug dosing with the smallest rate of adverse events as well as candidate agents for future host-directed therapies are described. Taken together, personalized medicine will provide opportunities to substantially improve the management and treatment outcome of difficult-to-treat patients with chronic respiratory infections.

Diagnosis and Management of Systemic Endemic Mycoses Causing Pulmonary Disease

“…Because of the variable bioavailability and the potential for drug-drug interactions, TDM is recommended, especially for patients who have severe disease, critically ill patients in intensive care unit, patients on multiple drugs including rifampicin and antiretroviral therapy with nonnucleoside reverse transcriptase inhibitors and protease inhibitors, and patients with infections of the central nervous system, eyes or bones. However, TDM is not universally available and several limitations have to be considered (e.g., assays are not standardized, optimal timing of sampling, sample transportation, unclear reference values) [55].…”

Pulmonary Diseases in Refugees and Migrants in Europe

“…Surgery should be considered in patients with single aspergillomas. A multidisciplinary approach could improve the management and treatment outcome of these difficult-to-treat patients with chronic pulmonary aspergillosis [78]. …”

Radiopathological Features and Identification of Mycobacterial Infections in Granulomatous Nodules Resected from the Lung

“…Japan remains a medium-burden tuberculosis country, with a tuberculosis incidence rate of 18 cases per 100,000 population according to the World Health Organization report in 2014 [7] . Compared with Europe and the United States, the latest reports from Japan also reveal a steady increase in the prevalence of nontuberculous mycobacteria (NTM) and the number of surgical resections for pulmonary disease [8][9][10] . It has thus become important to distinguish Mycobacterium tuberculosis (TB) from NTM for postoperative management, especially in patients with TB.…”