By adhering to epithelial cell surfaces, M. This propensity is stimulated by host immune defensins [ 94 ]. With a robust immune response, M. This interaction further promotes an airway inflammatory response. Despite this survival mechanism, the organism remains susceptible to most antibiotics used to treat respiratory tract infection. As many COPD exacerbations are associated with bacterial lung infections, patients with sputum cultures revealing S.
Acute exacerbation is elicited by bacterial virulence factors and the immune response to new infection. An important virulence factor in this setting is the polysaccharide capsule that mediates evasion from immune clearance. Capsular features may be helpful in identifying pathogenic potential of various pneumococcal species [ ]. The presence of S. In mixed culture, the risk of exacerbation does not appear to be elevated, which suggests that singular culture represents a more virulent species [ ].
Pneumococcal vaccines help reduce invasive infections caused by the many prevalent S. Although P. An increased prevalence of multi-drug resistant strains is observed in critically-ill patients [ , , ]. Exacerbations can be most readily attributed to P. The immune system responds by stimulating additional virulence factors from the P. Moreover, the presence of the mucoid phenotype may be observed in this setting, and, just as in CF, these mucoid strains persist in the lungs as biofilms Figure 8 , while non-mucoid strains may not.
The mucoid P. Figure 8: A. L-agar plate of mucoid P. View Figure 8. The biochemical and cellular derangements of CF produce innate immune system dysfunction. A normal component of innate lung defense is mechanical clearance of airway secretions by cilia on the epithelial cell surface [ - ].
Viscous mucus has several major consequences in the airway. First, as noted above, mucus compresses cilia against the cellular surface, and inhibits proper ciliary activity. Second, due to an already decreased clearance capacity, mucus directly interacts with the epithelial cell membrane. Over time, concentrated mucins directly anneal to the epithelial layer, and cannot be cleared by the cilia or by natural mechanical disruption e. These factors contribute to the characteristic mucus stasis and inflammation in the CF lungs A build-up of impacted mucus often begins at birth and continues throughout life in individuals with CF [ , ].
If it is not cleared, mucus forms an ideal niche that permits colonization by opportunistic microorganisms. Mucus plaque formation provides a surface on which bacteria adhere and form biofilms, which further increases plaque surface exopolysaccharide content, establishing a cyclical process of bacterial adherence, biofilm formation, and mucus plaque accumulation Figure 9.
Figure 9: Biofilms promote bacterial persistence during treatment. Planktonic bacteria can be cleared by antibiotics, antibodies, or host human cells. Once a biofilm has formed, these elements may become less effective. Enzymes utilized as part of phagocytosis build up within host cells and elicit cell damage and increased inflammation.
If bacteria return to planktonic form, the immune system and antibiotics are able to more effectively address infection. View Figure 9. A second underlying problem with immune responsiveness in CF patients is the abnormal degradation and cell trafficking of Toll-like Receptor 4 TLR4. Subsequently, the receptor is ubiquitinated and becomes associated with endosomes, where it activates INFR3 [ , , ]. These events contribute to the degradation of TLR4, and even subtle changes in this mechanism can perturb the immune response [ , - ].
Along with increased immunological responsiveness, these events may decrease TLR4 degradation, which further disrupts airway defense. CF also dramatically affects function and accumulation of phagocytes in lung tissues [ ]. Neutrophils, which accumulate to nearly fold above their normal levels, have impaired migration through the mucus in an attempt to clear bacteria before refractory biofilms are established, which may allow changes in the bacterial phenotype, including mucoid conversion of P.
Ineffective attempts at bacterial killing by neutrophils increase DNA deposition associated with neutrophil extracellular traps NETs , which further contribute to mucus viscosity.
Not only is the ability of neutrophils to phagocytose bacteria compromised, but steep oxygen gradients established by pathogens in airway secretions significantly impact generation of microbicidal reactive oxygen species ROS [ ]. Without ROS or reactive nitrogen species , neutrophil function is substantially compromised. Unlike CF airway, disease cigarette smoking is the major etiologic factor contributing to the development of COPD and this exposure elicits multiple innate immune system derangements Figure Cigarette smoke CS directly impairs mucociliary clearance [ ], including both ciliary shortening and physiologic function [ - ].
Direct cell death from CS exposure also leads to re-epithelialization that is dominated by goblet cells, a cellular compartment associated with mucus production [ , ]. Shortened cilia after CS exposure are associated with histone deacetylase 6-mediated selective auto phagocytosis and further degradation of cilia [ ]. Chronic reduction in mucociliary clearance promotes susceptibility to bacterial infection in patients with COPD, just as in CF.
Figure Smoking and the Immune System. View Figure CS also affects resident immune cells of the lung. These effects include increased numbers of alveolar macrophages and reduced ability to clear apoptotic cells and bacterial infections, due to impaired monocyte differentiation and lowered expression of surface recognition molecules [ , ].
CS also increases expression of pro-inflammatory chemokines and matrix metalloproteases, which suggest a change in macrophage chemokine phenotype [ , ]. Neutrophil ROS production regulates the phagocytic respiratory burst, and phagocytosis impairment during differentiation is another factor contributing to reduced bacterial clearance in COPD [ ]. Failure of neutrophil function is compounded by reduced antimicrobial capacity of macrophage apoptosis.
The polymorphonuclear cell derangements in COPD may also increase extravasation of lysozymes and granules into the extracellular space, contributing to pulmonary structural damage [ ]. Activity of natural killer NK cells, which normally contribute to eradication of viral pathogens, is increased by CS.
These activated NK cells may promote airway epithelial cell apoptosis and tissue damage due to dysregulated inflammation [ ]. Key aspects of CF treatment have traditionally focused on addressing symptoms of the disease, but more recently have included interventions directed towards correcting fundamental physiologic abnormalities caused by mutation of CFTR.
Symptomatic or palliative treatments, for example, include compensation for pancreatic insufficiency with supplemental pancreatic enzymes, high calorie diets with inclusion of fat-soluble vitamins, and anti-inflammatory agents to slow progression of respiratory function decline. General interventions for lung disease also encompass chest physical therapy and inhaled treatments to improve mucus clearance, together with antibiotic therapy for infection control [ ]. Failure of mucus clearance is a hallmark of CF pathogenesis, and a number of treatments have been developed to overcome this defect.
Mechanical devices and patient compliant actions chest physical therapy, aerobic exercise, etc. Treatments include use of active cycle breathing techniques and autogenic drainage, a breathing technique used to mobilize mucus up the airway, where it can be more easily cleared by coughing. Positive expiratory pressure masks and high frequency chest wall oscillation can aid in this process [ , ]. Prescription of these methods is typically provided on an individualized basis, as there is no evidence that one technique works more effectively in all cases [ ].
Furthermore, it is not established that use of airway clearing techniques is beneficial in the early stages of CF, when there may be little sign of lung impairment, and build-up of mucus is less pronounced. That being said, recent treatment guidelines often recommend daily airway clearance and aerobic exercise to help improve mucus clearance as a means to improve patient health [ ].
Mucolytic compounds are used to breakdown excess mucus lining the airways. In addition to airway secretions, themselves, DNA from neutrophil extracellular traps contributes significantly to increased CF sputum viscosity. Use of recombinant human DNase, such as dornase alfa, can be used to decrease viscosity and augment lung function [ , ]. Another useful mechanism is increased hydration of airway secretions. Newer modes of treatment aim to target basic genetic defects responsible for CF [ ].
Approaches using viral vectors - e. While early attempts towards CFTR replacement led to inadequate gene transmission and immune responses upon repeated administration [ ], technology in this area has continued to advance. Repeated nebulization of plasmid DNA and liposome complex [ ] in a double-blind study showed modest stabilization of lung function when the test group was compared to the control after one year.
Adverse events were noted in both study cohorts, with more serious effects observed after plasmid treatment. Gene transfer approaches such as these, as well as newer viral delivery vehicles, represent important areas for future investigation. More successful methods that aim to treat the underlying genetic cause of cystic fibrosis act on the mutant protein directly.
One example is the combination of lumacaftor and ivacaftor, two molecules that target the classic D variant [ ]. Lumacaftor is an agent known as a 'corrector'; it has been shown to partially 'correct' misprocessing of the Fdel mutant, increasing its presence at the cell surface [ ]. Ivacaftor acts to increase the probability that the CFTR channel is open, allowing for chloride and bicarbonate movement and proper function [ ].
Ivacaftor as a single drug has also shown robust benefit among numerous partial function CFTR mutations, for which the compound is FDA approved. Strategic antibiotic regimens are commonly used to control infection of CF airways, although resistance has become an increasing issue.
A large subset of these target P. Cystic fibrosis is inherited in a recessive pattern. Both parents must have copies of the defective gene and pass these defective copies down for the child to develop the condition, which affects around 30, people in the United States and 70, in the world. Individuals with CF develop a thick mucus that can block the airways in the lungs.
This mucus buildup results in troubled breathing and an increased susceptibility to respiratory infections, as mucus traps the bacteria and is unable to be removed efficiently. This condition also has severely debilitating effects on the digestive system, resulting in stunted growth and weight.
Because cystic fibrosis is a genetic disorder that affects so many organ systems, there is no existing cure, and patients must work closely with a team of healthcare professionals their whole life to manage their disease.
Most treatment protocols involve inhaled medication to thin the mucus in the airway, enzyme supplements to help with digestion and techniques for mucus removal. Although extremely draining and time-consuming, these protocols can greatly extend the length and improve the quality of life in CF patients. Some recent research has developed treatment that directly addresses the defective protein involved in CF. If you have more questions, or for more information about your specific condition, consult your physician.
To learn more about PF and other pulmonary conditions, visit these links:. Thank you to everyone Read more. This is called Read more. Have you or someone you know been recently diagnosed with Pulmonary Fibrosis?
If so, you probably have a lot of Read more. The theme for this week is self-advocacy. Self-advocacy means standing up for yourself, speaking up for your needs, or representing Read more. CF is caused due to a genetic defect and is diagnosed early in life, whereas COPD is generally caused due to lifestyle factors mostly smoking or other environmental exposures and is usually diagnosed after age Both these conditions would not generally coexist in one person.
Hello Harvard, both CF and pulmonary fibrosis are chronic lung diseases that progress over time. CF is caused due to a genetic defect and is diagnosed early in life, whereas pulmonary fibrosis is more often caused due to environmental exposures or is of unknown origin and is usually diagnosed in older people. Hello Edward, Most people do not generally talk about it due to embarassment, but COPD can cause incontinence particularly when a person is experiencing severe shortness of breath.
This is an automatic physical response. People with COPD may also experience incontinence while coughing, sneezing, laughing or during physical activity. As COPD progresses, the incontinence may become worse.
Wearing adult protective underwear, particularly when you are out, will help prevent the unpleasantness and fear associated with incontinence. Thank you for sharing and starting this conversation. Am I putting someone at risk with CF being around them if you have had Chronic Bronchitis in the past?
Am I putting them at risk? Hello Kirsten, thank you for reaching out to us. As you probably know, people living with CF are at a higher risk of getting lung infections because of the thick and sticky mucous buildup in their lungs. You must avoid close contact with them, particularly when you have an active infection. That is why making notes before your visit, as well as taking along a trusted family member or friend, may be helpful when talking to your doctor.
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