Article

Time to death, airway wall inflammation and remodelling in fatal asthma

Sir Charles Gairdner Hospital, Perth City, Western Australia, Australia
European Respiratory Journal (Impact Factor: 7.13). 10/2005; 26(3):429-34. DOI: 10.1183/09031936.05.00146404
Source: PubMed

ABSTRACT Fatal asthma is characterised pathologically by airway wall remodelling, eosinophil and neutrophil infiltration, accumulation of mucus in the airway lumen and smooth muscle shortening. The durations of fatal attacks of asthma show a clear bimodal distribution. Airway smooth muscle contraction and the accumulation of luminal mucus may contribute to death from asthma and relate to time to death. The current authors have examined these two components in uninflated lung tissue in cases of fatal asthma from the second Victorian asthma mortality study. Based on time from onset of symptoms to death, cases fell into two distinct groups: short course <3 (1.5+/-0.6 mean+/-sd) h; and long course >8 (12.3+/-5.9) h. Short course cases had more muscle shortening, higher levels of salbutamol and higher ratios of neutrophils to eosinophils than long course cases, who tended to have more mucus in the lumen. In conclusion, this study confirms the dichotomy of both time to death and the eosinophil/neutrophil ratio in cases of fatal asthma. It suggests that in short course cases acute airway narrowing is due, predominantly, to bronchoconstriction despite higher blood levels of salbutamol. Mucus accumulation may be more important in long course cases.

0 Followers
 · 
86 Views
  • Source
    • "Many structural changes occur in asthma, including epithelial shedding, enlarged submucosal glands, subepithelial basement membrane thickening and fibrosis as well as increased smooth muscle (Manuyakorn et al., 2013). The most striking change is in the smooth muscle which increases in amount by hyperplasia and hypertrophy, as well as spreading up and down the airway (James and Carroll, 2000), a mechanism for which remains unknown (James et al., 2005). Increasing smooth muscle contributes to airway wall thickness which is also driven by deposition of extra cellular matrix including collagen (Black et al., 2003; Howarth et al., 2004). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disorder of unknown etiology characterized by accumulation of lung fibroblasts and extracellular matrix deposition, ultimately leading to compromised tissue architecture and lung function capacity. IPF has a heterogeneous clinical course; however the median survival after diagnosis is only 3-5 years. The pharmaceutical and biotechnology industry has made many attempts to find effective treatments for IPF, but the disease has so far defied all attempts at therapeutic intervention. Clinical trial failures may arise for many reasons, including disease heterogeneity, lack of readily measurable clinical end points other than overall survival, and, perhaps most of all, a lack of understanding of the underlying molecular mechanisms of the progression of IPF. The precise link between inflammation and fibrosis remains unclear, but it appears that immune cells can promote fibrosis by releasing fibrogenic factors. So far, however, therapeutic approaches targeting macrophages, neutrophils, or lymphocytes have failed to alter disease pathogenesis. A new cell to garner research interest in fibrosis is the mast cell. Increased numbers of mast cells have long been known to be present in pulmonary fibrosis and clinically correlations between mast cells and fibrosis have been reported. More recent data suggests that mast cells may contribute to the fibrotic process by stimulating fibroblasts resident in the lung, thus driving the pathogenesis of the disease. In this review, we will discuss the mast cell and its physiological role in tissue repair and remodeling, as well as its pathological role in fibrotic diseases such as IPF, where the process of tissue repair and remodeling is thought to be dysregulated.
    Frontiers in Pharmacology 01/2013; 4:174. DOI:10.3389/fphar.2013.00174 · 3.80 Impact Factor
  • Source
    • "While cytokines such as IL-4 and IL-13 are crucial to production of IgE by B lymphocytes, others such as IL-5 are essential to eosinophil hematopoiesis, activation and survival in tissue. Numerous factors, including incense smoke, may contribute to the development of the Th1-Th2 imbalance [72-75], and the interaction between the innate and adaptive immune systems may lead to inflammatory changes and airway remodeling [76]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: In Asian countries where the Buddhism and Taoism are mainstream religions, incense burning is a daily practice. A typical composition of stick incense consists of 21% (by weight) of herbal and wood powder, 35% of fragrance material, 11% of adhesive powder, and 33% of bamboo stick. Incense smoke (fumes) contains particulate matter (PM), gas products and many organic compounds. On average, incense burning produces particulates greater than 45 mg/g burned as compared to 10 mg/g burned for cigarettes. The gas products from burning incense include CO, CO2, NO2, SO2, and others. Incense burning also produces volatile organic compounds, such as benzene, toluene, and xylenes, as well as aldehydes and polycyclic aromatic hydrocarbons (PAHs). The air pollution in and around various temples has been documented to have harmful effects on health. When incense smoke pollutants are inhaled, they cause respiratory system dysfunction. Incense smoke is a risk factor for elevated cord blood IgE levels and has been indicated to cause allergic contact dermatitis. Incense smoke also has been associated with neoplasm and extracts of particulate matter from incense smoke are found to be mutagenic in the Ames Salmonella test with TA98 and activation. In order to prevent airway disease and other health problem, it is advisable that people should reduce the exposure time when they worship at the temple with heavy incense smokes, and ventilate their house when they burn incense at home.
    Clinical and Molecular Allergy 02/2008; 6(1):3. DOI:10.1186/1476-7961-6-3 · 1.39 Impact Factor
Show more

Preview

Download
0 Downloads
Available from