nemoci-sympt/BAKTERIALNI-INFEKCE/chlamydie/symptomy-a-asociovana-onemocneni/astma
Astma
- Různé typy a příčiny astmatu
Atopic (extrinsic)
- Větší roli dědičnost a prostředí [22]
Nonatopic (intrinsic)
- Typically has its onset in adulthood
- Po respirační infekci !!!
- More severe clinical course than atopic asthma
- Not closely associated with family history
- Different aetiological mechanisms [22]
Probably able to cause persistent infections - associated to asthma
- Adenovirus
- Respiratory syncytial virus (RSV)
- Mycoplasma pneumoniae
- Chlamydia pneumoniae [22]
- Extensive data exist for C. pneumoniae
- Appears to involve multiple genes
C.p. and Astma
- Asthma bronchiale
- Chronická obstrukční plicní nemoc (CHOPN)
- Významnou měrou se podílí na akutních exacerbacích asthma bronchiale i CHOPN
- Bronchogenní karcinom
- Sarkoidóza
- Signifikatně vyšší detekce mikroba u astmatiků v bronchiální stěně
- Oproti jiným respiračním onemocněním
- Vysoké titry protilátek proti C. pneumoniae jsou u nich spojeny s výraznějšími klinickými obtížemi
- Intenzivní příliv neutrofilů u těžkého astmatu
- Potentním zdrojem proteolytických enzymů schopných poškozovat a aktivovat epitel dýchacích cest
- Neutrofilní elastáza může vyvolávat degranulaci eozinofilů
- C. pneumoniae tak mohou akcelerovat zánět i poškození dýchacích cest způsobené již vlastním astmatem
- Granulocyty - hlavní cílové buňky pro C. pneumoniae
- Následně proměněny v jakýsi „infekční rezervoár“
- A nosičů pro překonání bariér
- Strong quantitative association between the antibody level to C. pneumoniae and wheezing [22]
- Elevated specific antibody levels - significantly associated with asthmatic bronchitis
- After, rather than before, respiratory illness
- C. pneumoniae infection - a newly diagnosed asthma was recorded [22]
- Astma significantly associated with elevated IgG levels to C. pneumoniae [22]
- Even stronger association with long-standing asthma among the nonatopics [22]
- Elevated IgG and/or IgA antibody levels to C. pneumoniae significantly associated with severe chronic asthma [22]
- C. pneumoniae-specific secretory IgA antibodies in nasal aspirates
- More than seven times higher in those children who reported at least four exacerbations during 13 months
- Than in those reporting only one episode [22]
- C. pneumoniae has also been found to cause ciliostasis in bronchial epithelial cells in vitro
- Appears to be a specific property of C. pneumoniae [22]
Chlamydia pneumoniae
- Persist and cause chronic infections
- May be associated with asthma
- Can achieve a state of “latency”
- Viable but dormant and does not multiply
- Continues to synthesize the “stress” protein - hsp60
- Able to elicit a strong host inflammatory response at sites of its production
- Appears to be involved in tissue injury and scarring processes [22]
- Inflammation present in almost all asthmatics
Acute viral infections
- Well-established triggers of asthma exacerbations among both adults and children
- ?80% of acute exacerbations may be caused by viruses [22]
Epithelial cell injury in asthma
- Airway remodelling
- Fundamental feature of asthma
- Disruption and altered function of the epithelium in asthmatics
- Cause of stimuli
- Lead to restructuring of the airway wall
- As a response to injury
- Inflammation and the associated healing process
- Scar formation
- Tissue remodelling
- Present in almost all asthmatics irrespective of disease severity, aetiology or duration of disease [22]
- Epithelial cells in asthmatics
- Reduced capacity to repair the epithelial layer following injury
- Enhanced capacity to produce proinflammatory and profibrogenic cytokines
- Central role in the coordination and sustenance of the inflammation
- Maintaining the chronic inflammatory process
- Initiate it 24.inflammation [22]
- Complex interactions
- Role of a persistent infection here cannot be ignored !!! [22]
Association between asthma and C. pneumoniae infection
- First put forward by Hahn et al. in the early 90’s
- Since then, evidence has accumulated both for paediatric and adult populations
Children:
- Acute infection with atypical pathogens and acute asthma exacerbations in children
- Vast majority of studies were concordant in finding an association
- C. pneumoniae identification varied between 4.5% and 25% of asthma episodes
Adults:
- Acute atypical infection and asthma exacerbations
- More severe functional impairment on admission
- Slower FEV1 rise during follow-up when compared with the group without acute infection [25]
- Sero-epidemiological studies
- Many asthmatics have elevated antibody levels to C. pneumoniae [25]
Use of Antibiotics in Asthma Patients with C. pneumoniae Infection
- C. pneumoniae eradication from the airways would become an important aspect of asthma treatment
- Macrolides, the ketolide telithromycin, tetracyclines and fluoroquinolones would be logical candidate drugs
- Clinical trials in children and adults with asthma
- Mostly employed macrolides due to their
- Favorable tolerability/safety profile
- Excellent intracellular accumulation characteristics [25]
- A Cochrane review of macrolide usage in chronic asthma
- Overall positive effect on symptoms and eosinophilic markers of inflammation following macrolide therapy [25]
- Multicenter, double-blind, randomized, placebo-controlled clinical study assessed oral telithromycin
- As a supplement to standard of care treatment for adults with acute asthma exacerbations
- Ketolide treatment was associated with statistically significant and clinically substantial benefits
- 61% of patients had evidence of C. pneumoniae and/or M. pneumoniae infection
- Effect of telithromycin on FEV1 was statistically significant
- no differences between infection-positive and -negative groups in terms of other study outcomes [25]
- Main limits
- Patient populations size
- Prevalent use of serology as the applied diagnostic test [25]
C.Pneumoniae specific IgE is prevalent in asthma and is associated with disease severity
- Hahn et al, 2012 [153]
