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Hong Wei Chu M.D.
Telephone: 303-398-1689
Hong Wei Chu

Hong Wei Chu, M.D.
National Jewish Medical and Research Center
1400 Jackson Street
Denver, Colorado 80206
USA alicante Car hire airport Alicante.

Research Interests:

  1. Asthma immunopathology and molecular pathology
  2. Mycoplasma pneumoniae and Chlamydia pneumoniae in the pathogenesis of chronic asthma
  3. Airway remodeling in asthma


  1. Wenzel SE, Schwartz LB, Langmack EL, Halliday JL, Trudeau JB, Gibbs RL and Chu HW. Evidence that severe asthma can be divided pathologically into two inflammatory subtypes with distinct physiologic and clinical characteristics. Am J Respir Crit Care Med 1999;160(3):1001-1008

  2. Chu HW, Halliday JL, Martin RJ, Leung DY, Szefler SJ and Wenzel SE. Collagen deposition in large airways may not differentiate severe asthma from milder forms of the disease. Am J Respir Crit Care Med 1998;158(6):1936-1944

  3. Chu HW, Wang JM, Boutet M, Boulet LP and Laviolette M. Immunohistochemical detection of GM-CSF, IL-4 and IL-5 in a murine model of allergic bronchopulmonary aspergillosis. Clin Exp Allergy 1996;26(4):461-468

  4. Chu HW, Wang JM, Boutet M and Laviolette M. Tumor necrosis factor-alpha and interleukin-1 alpha expression in a murine model of allergic bronchopulmonary aspergillosis. Lab Anim Sci 1996;46(1):42-47

  5. Chu HW, Wang JM, Boutet M, Boulet LP and Laviolette M. Increased expression of intercellular adhesion molecule-1 (ICAM-1) in a murine model of pulmonary eosinophilia and high IgE level. Clin Exp Immunol 1995;100(2):319-324

For a list of all publications since 1986, click here.

Asthma: Etiology and Inflammation

The Carl and Hazel Felt Laboratory for Asthma Research

The investigations in our laboratory have focused on several aspects of asthma. These include: 1. the potential role of Mycoplasma pneumoniae and Chlamydia pneumoniae in the etiology of asthma; 2. the circadian aspect of the inflammatory response and its effect on steroid resistance; and 3. expired nitric oxide in evaluating the asthma response.

1. Mycoplasma and Chlamydia in Asthma
This project deals with the concept that a bacterial process (mycoplasma and/or chlamydia) is involved in the pathogenesis of chronic asthma. Presently, we have found by polymerase chain reaction (PCR) that 51% (20/39) asthmatics have M. pneumoniae or M. fermentans-M. genitalium (n=1) in their airways. In healthy control subjects only 9% (1/11) was positive (p=0.007). PCR for Chlamydia pneumoniae was positive in 7/39 asthmatics and 0 controls. Enzyme immunoassay (EIA) for respiratory viruses were negative in all subjects. Treatment of asthmatics with either placebo or clarithromycin is ongoing. In those asthmatics on clarithromycin, there is a significant increase in FEV1 which is not seen on placebo. Of interest, using only PCR positive subjects, the increase in FEV1 was 260 ml (p=0.03) on clarithromycin while PCR negative subjects had a nonsignificant increase of 120 ml (p=0.29) with the antibiotic. Furthermore, the PCR positive group had a trend to decreased lymphocytes in the BAL (p=0.06).

Additionally, our findings have shown that asthmatics studied from this population have increased neurogenic inflammation (Substance P and NK-1) which decreases on clarithromycin treatment compared to placebo. Also, we have now been successful in demonstrating the efficacy of a new polyclonal antibody to M. pneumoniae. This comes from our work using a pure culture and in an infected mouse model. This will now allow us to use this as another check for mycoplasma in the airways of asthmatics.

The mycoplasma "prevalence" project will continue as well as the following: development of competitive PCR to evaluate the mycoplasma burden; antibody fluorescent staining for electron microscopy analysis of mycoplasma; the local immune response; T-lymphocyte populations and cytokines felt to be involved in infectious and asthmatic processes; and evaluation of angiogenesis on histologic samples.

If 50% of asthmatics have mycoplasma and/or chlamydia localized to their airways, this will be a major advancement in understanding the pathogenesis of asthma in this subset. It is important to understand that our ability to treat this organism is not absolute and future studies will include a multiple drug schedule.

2. Steroid Resistance
Nocturnal worsening of pulmonary function is a common and potentially serious complication of asthma as 70% of deaths from asthma occur during the nighttime hours. We have shown that asthmatics who experience nocturnal worsening have greater airway inflammation at 4 am than at 4 pm illustrated by increased number of neutrophils, eosinophils and lymphocytes in the lungs at 4 am. The mechanisms for heightened nocturnal inflammation are not well understood. Neurohormonal changes, including cortisol activity and sensitivity to cortisol are thought to play a role in controlling endogenous allergic tissue inflammation.

Cortisol and other glucocorticoids (GC) exert their effects by binding to the glucocorticoid receptor (GR) and translocating to the nucleus where it binds to transcription factor modulating glucocorticoid responsive genes. Previous studies from our group on nocturnal asthma (NA) and GC insensitive asthma have demonstrated an association between GR abnormalities and poor response to steroids. Glucocorticoid receptor-beta (GR-β) is an alternative form the glucocorticoid receptor formed by alternative splicing. GR-β has been shown to be increased in patients with steroid resistant asthma and induced by the cytokines interleukin (IL)-2 and IL-4; thus, it may provide a mechanism for reduced steroid responsiveness. We hypothesized that airway cells would demonstrate decreased steroid responsiveness at night in nocturnal asthmatics as compared to subjects without nocturnal worsening of lung function. Increased expression of GR-β at night in NA may provide a possible mechanism.

In the present study, we have shown for the first time that airway cells from subjects with asthma exhibit a circadian variation in steroid responsiveness. This was illustrated by the decreased ability of corticosteroids to suppress production of cytokines from BAL macrophages and proliferation of lymphocytes at particular times of day. In addition, the expression of GR-β was increased at night in subjects with NA along with the expression of IL-2 and IL-4 mRNA, but there was no difference in GR-β or cytokine mRNA expression within the non-NA group.

We conclude that improved knowledge of steroid responsiveness may be important in understanding the pathogenesis of asthma. Reduced steroid responsiveness appears to be present even in milder asthmatics and not considered severe by clinical criteria. These observations may explain why a spectrum of responses of antiinflammatory therapy occurs in asthma. Further studies are necessary to determine the specific cell characteristics and the mechanisms causing this interesting and clinically relevant phenomenon.

3. Nitric Oxide
Nocturnal asthma is a serious and common problem accounting for morbidity and mortality. However, our knowledge of the chronopathology of asthma is far from complete. Airway inflammation is augmented at night in NA and is correlated with decrements in lung function. The assessment of airway inflammation has depended until now on invasive techniques, such as bronchoscopy and the analysis of induced sputum, both of which are time-consuming, costly and can worsen lung function. The measurement of exhaled mediators, e.g., exhaled nitric oxide (ENO), may allow the repeated non-invasive assessment of airway inflammation as ENO is high in untreated asthma and falls rapidly after therapy with corticosteroids.

Our investigation has demonstrated that ENO unexpectedly fell significantly in nocturnal asthma from 4 pm (77.2 ± 8.2 ppb) compared to 10 pm (68.4 ± 8.7 ppb, p<0.003) and 4 am (66.0 ± 8.5 ppb, p<0.001) with no significant difference between 10 pm and 4 am. In contrast, there were no significant differences in mean ENO at 4 pm, 10 pm and 4 am in non-nocturnal asthma (51.3 ± 10.8, 57.7 ± 13.4, 53.8 ± 12.5 ppb, respectively). Following bronchodilator, ENO rose significantly by 10.5 ± 1.8 ppb in the nocturnal asthma group alone. Thus, the circadian rhythm of ENO differed greatly between nocturnal and non-nocturnal asthma. The significant decrease in ENO in nocturnal asthma may reflect an important chronobiological defect in the endogenous production and/or increased disposition of nitric oxide which, in view of its bronchodilator action, could play a role in nocturnal exacerbations of asthma.

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