Respiratory System

The respiratory system is a collection of tissues and organs that allows for gas exchange, primarily by absorbing oxygen and releasing carbon dioxide. The respiratory system is broken up into two main sections, the upper and lower respiratory tracts. The upper respiratory tract is contained in the head and neck, consisting of the nasal passages, sinus cavities, pharynx, and larynx. The nasal passages act as tunnels through which air is drawn or pushed, and they house the olfactory receptors that enable the sense of smell. The nasal passages connect to the sinus cavities (air-filled spaces) within the bones of the skull, through which the human voice resonates. The nasal passages continue past the sinus cavities and through the glottis (the throat diaphragm). The glottis manipulates the air pushed out of the lungs during speech.

The lower respiratory tract is contained entirely within the thorax, the part of the body between the neck and abdomen, and is made up of the lungs, bronchi, bronchioles, and alveoli. Air enters the nasal cavities, passes through the sinuses into the pharynx, and then air enters the trachea. The trachea is a cartilaginous tube that acts as an air conductor. The trachea then splits into right and left primary bronchi, secondary bronchi, tertiary bronchi, before entering the tissue of the lung as terminal bronchioles. At the end of each terminal bronchiole are groups of sac-like structures called alveoli. Gas exchange occurs in the alveoli. Oxygen is absorbed into the blood, and carbon dioxide is released into the lungs. For gas exchange to occur, respiratory tissue in the lungs must remain moist so that oxygen can dissolve in fluid and pass into the blood. Moisture levels in the lungs are maintained by a thick layer of mucus that is constantly produced and degraded by lung tissues. The mucociliary escalator is a barrier preventing infection that lines the lower respiratory tract, where cilia, microscopic hairlike cellular structures, rhythmically beat mucus up toward the throat. Mucus lining the lower respiratory tract has two layers: a sol layer and a gel layer. The upper gel layer is made by goblet cells, and contains antibodies, immune cells, and chemicals to destroy bacteria and viruses. A goblet cell is a simple columnar epithelial cell that secretes mucus to protect the mucous membrane. The sol layer is thinner and surrounds the cilia. Irritants in the nasal passages, lungs, and throat can be mechanically removed through coughing and sneezing. The mucus lining functions as a surfactant, a chemical agent that reduces surface tension. Surfactants cause particulate matter (or individual microbes within a colony) to move away from each other, which allows other chemical agents to act on irritants or pathogens. The cells lining the respiratory tract also produce a collection of immune modulators, such as antibodies, proteins that recognize and bind to specific antigens; phospholipoprotein surfactants that decrease surface tension of liquid; and reactive oxygen species, chemicals containing oxygen that are easily reactive to other chemicals in the cell, to protect from pathogens. Alveolar macrophages, a type of white blood cell in the lungs, clear the air of infections, toxins, or allergens that have passed by the respiratory system's physical defenses. Alveolar macrophages use phagocytosis, a process by which cells engulf and digest pathogens or other material, and intracellular killing to clear out the air.

Both the upper and lower respiratory tracts are colonized by distinct microbial communities, called the respiratory microbiome, that take advantage of the moist, warm environment that is constantly exposed to the outside world through the nonsterile air drawn through the airways. As such, dozens of microbial species are adapted to the unique environments within and can play both positive and negative roles in human health. Similar to the gut microbiota, microbial communities in the respiratory system are dominated by bacteria, the most abundant of which are members of the phyla Firmicutes and Bacteroidetes.

The bacterial species that make up the lung and nasal microbiomes vary considerably between different people, which is generally due to new bacterial species constantly being introduced by such close contact with the oral microbiota, microorganisms found in the oral cavity, and as people breathe naturally. An association between childhood exposure to microbes and the subsequent development of asthma has been observed. In general, having a greater exposure to bacteria and increased diversity in the respiratory and gastrointestinal system are protective against asthma. However, certain pathogenic bacterial species found in the respiratory microbiome have been shown to be positively associated with asthma.

There have also been associations made between the microbiota of the respiratory system and diseases like chronic obstructive pulmonary disease (COPD), cystic fibrosis, and pneumonia. In its early stages, COPD patients show very little difference in their lung microbiota from people without the disease. It is not until COPD progresses to its severe stage where evidence of a change in the microbial species is evident. Recent studies have suggested that fungal growth in the lungs may be a contributing factor to the disease. Cystic fibrosis has long been known to affect the microbiota of the lungs. There is significant evidence that all cystic fibrosis patients grow pathogens as early as adolescence. Studies into the microbiota of pneumonia have been challenged because it was originally thought the lungs were a sterile environment. Healthy patients have show colonization of inert, or inactive, pathogens, and the growth of select potential pathogens in the lung environment is promoted by features of host inflammatory defenses. This creates a positive feedback loop that encourages the reproduction of these pathogens and overpopulation of the lungs by the microbiota.

Genera such as Prevotella, Veillonella, and Streptococcus are almost universal respiratory colonizers, species that spread to new areas, among humans. Prevotella is a genus of gram-negative bacteria that is commonly associated with the oral and nasal microbiomes but is also capable of causing pneumonia under certain circumstances. Streptococcus pneumoniae is a species of gram-positive bacteria commonly found in the nasal passages. Staphylococcus aureus is a species of gram-positive bacteria commonly found on the skin and in the respiratory tract. Streptococcus pneumoniae and Staphylococcus aureus are two common examples of opportunistic pathogens, or organisms that colonize the respiratory tracts of healthy people but occasionally cause disease when conditions are right for infection. Other common members of the respiratory microbiota include Sphingomonas, Pseudomonas, Fusobacterium, and Megasphaera.