About Progressive Pulmonary Disease (PPD)
Frequent pulmonary exacerbations and hospitalizations are a hallmark of cystic fibrosis (CF) and other progressive pulmonary diseases. The pathogenic disease mechanism is set in motion by a cascade of underlying structural and functional factors:
- Changes to the pulmonary epithelia lead to mucus abnormalities that trigger adherence of bacteria.
- The lack of bacterial clearance in turn causes infection leading to biofilm accumulation, inflammation and airway clogging.
- Frequent pulmonary exacerbations are difficult to treat because biofilms enhance antibiotic resistance.
- This contributes to the progression of pulmonary decline in cystic fibrosis and other respiratory diseases, and ultimately lead to overwhelming symptoms, impact on quality of life (QoL), and debilitating progressive lung disease.
PPD destroys the foundation of lung function, having a dramatic impact on how people live their life.
Quick Facts About Non-Tuberculosis Mycobacteria (NTM)
Non-tuberculous mycobacteria (MTM) is found in the environment (soil and water) and can lead to serious lung infections. Non-tuberculous mycobacteria are naturally-occurring organisms that can cause pulmonary infections when an individual inhales the organism from their environment. NTM lung infection is a slowly progressive, difficult to treat, and destructive lung disease.
- NTM is a threat to patients with lung disease since it is a chronic, debilitating condition that can significantly increase patient morbidity and mortality.
- NTM drives pulmonary deterioration, and rapid decline in pulmonary function.
- The most common organism associated with these infections is Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex (MABSC). MAC accounts for more than 80% of all NTM lung disease cases.
- Certain underlying comorbidities and conditions make some people susceptible to NTM infection: prior lung infection, cystic fibrosis, primary ciliary dyskinesia and certain people with bronchiectasis.
- NTM is assembled in biofilm colonies in the mucus and alveolar walls in lung tissue.
Quick Facts About Burkholderia Complex
Burkholderia cepacia complex (BCC) bacteria in cystic fibrosis (CF) patients generally leads to a more rapid decline in pulmonary function, and often to fatal necrotizing pneumonia known as the “cepacia syndrome.”
- BCC results in rapidly progressive, invasive, fatal bacteremic disease.
- BCC has a high potential for patient-to-patient spread, both within and outside the hospital.
- BCC organisms are difficult to eradicate due to innate resistance to a range of antibiotics and their innate capacity to form biofilms, making them extremely difficult to treat once they infect the lungs.
- ~20 different BCC species exist, with some more harmful than others (B cepacia, B. cenocepacia and dolosa).
- BCC infections present a significant challenge for people with CF.
- The clinical course of cepacia infections is variable, but infection is typically chronic and ∼20% of patients eventually succumb to the cepacia syndrome.
Quick Facts About Pseudomonas aeruginosa & Methicillin Staphylococcus aureus (MRSA):
Chronic Debilitating Pathogens in Pulmonary Disease
Pseudomonas aeruginosa (PA) and MRSA are major causes of lung infections in CF, PCD and certain people with non-CF bronchiectasis.
- PA develops resistance in the lungs and form biofilms, rendering ineffective clearance by immune defense systems and antibiotics. Over time, PA infection causes inflammation and damage to the lungs that won’t go away.
- Once Pseudomonas is colonized it’s difficult to eliminate, leading to progressive lung disease.
- When CF patients’ lungs are infected with PA, they experience worsening symptoms such as coughing, wheezing, and mucus production — all of which make it harder to breathe.
- Methicillin Staphylococcus aureus (MRSA) is challenging to eradicate as it also forms protective biofilms in the lungs that further reduce its susceptibility to antibiotics.
- The incidence of MRSA in CF has increased dramatically, contributing to progressive lung disease.
- MRSA is associated with worse outcomes relative to CF patients without MRSA, or to those in whom the infection was eradicated.
- Increased use of oral, inhaled, intravenous antibiotics and hospitalization rates.
- Significant decline in lung function (FEV1).
- Higher risk of failing to recover to baseline levels after pulmonary exacerbations.
- Increase in mortality.