This book reviews the role of the lung microbiome in the development and progression of lung diseases. It deals with the role of microbiota dysbiosis in influencing host defense and immunity leading to resistance, colonization, and disease exacerbation. The book delineates the complex interaction between pathogen and lung residual microbiota during disease conditions. It further highlights the potential role of lung microbiota as the key modulator of lung carcinogenesis and immune response against cancer cells. Lastly, it reviews technological developments for unraveling the lung microbiome that profoundly impacts clinical diagnostics. This book is an essential resource for the scientists working in pulmonary diseases, pharmaceutical & clinical sciences, and pulmonary clinicians.

Studying the lung microbiome requires a specialist approach to sampling, laboratory techniques and statistical analysis. This Monograph introduces the techniques used and discusses how respiratory sampling, 16S rRNA gene sequencing, metagenomics and the application of ecological theory can be used to examine the respiratory microbiome. It examines the different components of the respiratory microbiome: viruses and fungi in addition to the more frequently studied bacteria. It also considers a range of contexts from the paediatric microbiome and how this develops to disease of all ages including asthma and chronic obstructive pulmonary disease, chronic suppurative lung diseases, interstitial lung diseases, acquired pneumonias, transplantation, cancer and HIV, and the interaction of the respiratory microbiome and the environment.

This book comprehensively covers the microbiome in respiratory disease, from the initial research study to the disease-specific implications and related applications. Research on the respiratory microbiome is increasing in volume and scope. This reflects rapidly growing interest in the study of respiratory disease to understand how microbiota shape mechanisms of disease pathogenesis. The respiratory tract spans the nasal passages, sinus cavities, oropharynx, and the tracheobronchial tree of the lungs. In these compartments of the upper and lower respiratory tract, the microbiota have now been studied in the context of several chronic respiratory conditions. These include chronic sinusitis, allergic rhinitis, asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis and pulmonary fibrosis, to name a few. The potential impact of ecological interactions (i.e., between microbes and between microbiota and host) within and across respiratory compartments is increasingly recognized. The book is organized into two main sections. Part I, Principles and Tools, covers conceptual modeling of the respiratory microbiome, experimental methodology with a focus on a priori considerations in study design and sampling, laboratory and computational methods for analysis of respiratory microbiome data, and minimizing interpretive pitfalls. Part II, Applications, discusses the evidence from specific studies that have shed novel insights into the influence of respiratory microbiota on mechanisms or outcomes in specific diseases. Based on current best evidence, disease-specific chapters include chronic rhinosinusitis, asthma (pediatric and adult studies), chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), bronchiectasis not due to CF, idiopathic pulmonary fibrosis, and lung transplant. This is an ideal reference for forward-thinking practitioners with interest in novel developments in precision medicine applications in lung disease, as well as translational scientists in the field of microbiology, immunology and lung biology.

Dr. Fasano holds stocks in Alba Therapeutics and receives financial support from Takeda Pharmaceuticals. Dr. Taneja receives financial support from Elysium Health and Evelo Biosciences. The other Topic Editors declare no competing interests with regards to the Research Topic subject.

Respiratory diseases are leading causes of death and disability globally, with about 65 million people suffering from COPD, and 334 million from asthma, the most common chronic disease. Each year, tens of millions of people develop and can die from respiratory infections such as pneumonia and TB. Systemic inflammation may induce and exacerbate local inflammatory diseases in the lungs, and local inflammation can in turn cause systemic inflammation. There is increasing evidence of the coexistence of systemic and local inflammation in patients suffering from asthma, COPD, and other lung diseases, and the co-morbidity of two or more local inflammatory diseases often occurs. For example, rheumatoid arthritis frequently occurs together with, and promotes the development of, pulmonary hypertension. This co-morbidity significantly impacts quality of life, and can result in death for those affected. Current treatment options for lung diseases are neither always effective, nor often condition-specific; there is a desperate need for novel therapeutics in the field. Additionally, the molecular and physiological significance of most major lung diseases are not well understood, which further impedes development of new treatments, especially in the case of coexistent lung diseases with other inflammatory diseases. Great progress has been made in recent years in many areas of the field, particularly in understanding the molecular geneses, regulatory mechanisms, signalling pathways, and cellular processes within lung diseases, as well as basic and clinical technology, drug discovery, diagnoses, treatment options, and predictive prognoses. This is the first text to aggregate these developments. In two comprehensive volumes, experts from all over the world present state-of-the-art advances in the study of lung inflammation in health and disease. Contributing authors cover well-known as well as emerging topics in basic, translational, and clinical research, with the aim of providing researchers, clinicians, professionals, fellows, and students with new perspectives and concepts. The editor hopes this book will also help to direct future research in lung disease and other inflammatory diseases, and result in the development of novel therapeutics.

Vast and diverse microbial communities (the microbiome) are distinct at different human body sites and strongly influence health and disease. Specifically, the respiratory tract microbiome is thought to influence outcomes after lung transplantation, the only therapeutic option for end-stage lung diseases. Studies dissecting the role of the microbiome on pulmonary health should also include the viral microbiome (virome), which is less-studied due to unique challenges in identifying these small, diverse, self-replicating genetic elements. Organ transplantation is accompanied by immunosuppression, which can result in reactivation of latent viruses, transfer of viruses from organ donor to recipient, and increased susceptibility to viral infections. We therefore used high-throughput metagenomic approaches to study the virome of lung transplant recipients (LTRs). We first characterized the virome in LTRs and its relationship to clinically defined adverse events. We discovered that a family of eukaryotic viruses (Anelloviridae) is abundant in the lung and blood of LTRs and that their levels in the lungs were associated with primary graft dysfunction, a form of acute lung injury. Next, we investigated the temporal and spatial dynamics of the virome during lung transplantation and identified herpesviruses, parvoviruses, polyomaviruses, bacteriophage and complex anellovirus populations. We focused on the abundant anelloviruses by assembling genomes from shotgun metagenomic sequences and tracking their representation in the lung and blood of LTRs post-transplantation using a metric that accounts for inter-and intra-subject viral diversity. This analysis revealed that anellovirus populations move between lung allografts and the peripheral blood of LTRs. However, many uncharacterized sequences still existed in the metagenomic data generated in these studies. To address this, we developed a molecular and bioinformatics pipeline to mine public datasets and discovered a novel family of small, circular DNA viruses (Redondoviridae). Quantification of redondoviruses in human oro-respiratory samples showed an association with periodontal disease and acute illness. Overall, this work helps define the virome during lung transplantation and introduces a new family of human viruses, broadly demonstrating the importance of exploring the human virome.