Why hypoxia in asthma

Persistent hypoxemia after an asthma attack. Ultrasound J 11, 6 Download citation. Received : 21 November Accepted : 27 February Published : 21 March Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search all SpringerOpen articles Search. Download PDF. Abstract The presence of an unknown intracardiac shunt due to a patent foramen ovale may be an unusual cause of hypoxemia.

Case presentation A year-old woman was admitted to the emergency department with a severe asthma attack. Full size image. Discussion Patent foramen ovale is involved in many clinical situations, including cryptogenic stroke, decompression sickness, migraine, massive pulmonary embolism and acute cor pulmonale [ 3 , 4 ]. Conclusions In conclusion, the presence of PFO should be highly suspected and looked for as potential cause of unexpected persistent hypoxemia after severe acute asthma attack; echographic evaluation represents an important bedside tool during diagnostics of critically ill patients with unexplained persistent hypoxemia.

References 1. Echocardiography — Article Google Scholar 7. Echocardiography — Article Google Scholar 9. Competing interests The authors declare that they have no competing interests.

Availability of data and materials Original data files are available upon request. Consent for publication Informed consent for publication of completely anonymous data was obtained from the patient. Ethics approval and consent to participate No ethical approval was needed for this case report.

View author publications. Additional file. Additional file 1. Something went wrong on our side, please try again. Show references Theodore AC. Oxygenation and mechanisms of hypoxemia. Accessed Nov. Wilkinson JM expert opinion. Mayo Clinic, Rochester, Minn. Rochester, Minn.

Broaddus VC, et al. Acute hypoxemic respiratory failure and ARDS. Philadelphia, Pa. Vincent JL, et al. Arterial hypoxemia. In: Textbook of Critical Care. Strohl KP. Overview of obstructive sleep apnea in adults. Wilkins MR, et al. The tube-forming sprout outgrowth assay was performed as previously described [24].

At least 10 spheroids per gel were embedded within fibrin gels in well plates. After incubation for 24 h, spheroids were fixed in-gel, stained with TRITC-conjugated phalloidin Sigma-Aldrich, Buchs, Switzerland and sprout outgrowth from each spheroid was quantitated by morphometric analysis of the length of outgrowing tubules [24]. Figure 1 presents a typical example of a human airway tissue cross-section demonstrating the increased thickness of the basement membrane present in non-asthma Figure 1A relative to asthma Figure 1B subjects.

Note the increased thickening of the basement membrane in the asthmatic airways. No differences were observed between the asthmatic and non-asthmatic subjects. The experiments shown are representative for 5 independent experiments. Similarly, under the same conditions the release of IL-6 protein increased in both asthmatic and non-asthmatic cells 5. Under the same conditions the release of IL-6 protein increased in both asthmatic and non-asthmatic cells 2. The effect of hypoxia on the release of IL-8 was less pronounced, but significant 2.

Hypoxia did not affect the release of ENA significantly 0. No significant differences were observed between asthmatic and non-asthmatic BSMC in any condition. Spheroids were also cultured in unconditioned medium i. Figure 5 shows representative images of spheroids incubated with CM from BSMC grown under normoxic left panel or hypoxic right panel conditions. B, lengths of sprouts outgrowing from every spheroid were measured and the mean of the longest 10 sprouts of 7 randomly chosen spheroids was plotted.

Finally, we sought to define the mechanism involved in the aforementioned findings. We examined the effect of hypoxia on pooled CM, derived from asthmatics and non-asthma controls.

CM from non-asthma controls did not show any difference whether BSMC were grown under hypoxic or normoxic conditions. In contrast, CM from asthmatics significantly increased the sprout outgrowth from EC spheroids comparing normoxia Hypoxia of the airways can be caused by a range of mechanisms, including diminished ventilation drive, airway obstruction, intra-alveolar exudates, airway wall inflammation, as well as fibrosis and basement membrane thickening [25].

The latter is one of the striking features of the asthmatic airway wall and may well contribute to locally restricted hypoxia. This may in turn affect the properties of resident cells present in the airway wall. Biopsy studies in adults and children showed a significant increase in the number of micro-vessels present in the airway wall of asthma patients and there is evidence that endothelial cells undergo proliferation [26] — [28].

In our current study, we showed that hypoxia has a profound effect on the proliferation of and angiogenic factors released by primary human BSMC of both asthmatic and non-asthmatic subjects. First, hypoxia has the capacity to significantly reduce the proliferation rate of BSMC of both asthmatic and non-asthmatic subjects. This indicates that BSMC of asthmatics are more responsive to hypoxic environments compared to non-asthmatics.

The reason for this difference is unclear, but it might reflect diminished proliferation control responses as observed in cultured asthmatic BSMC [2] — [5] , [29]. Our data also indicate that the effects of hypoxia may be distinct in different model organisms, since it has been demonstrated that BSMC of rats have significantly increased proliferation rates under hypoxic conditions [30].

The reason for this discrepancy between primary human BSMC and those of rats is currently not known. Second, our study showed that hypoxia enhanced the release of VEGF, a mediator of micro-vascular leakage, EC proliferation and vascular remodeling, as well as IL-6 and IL-8, which are known to be involved in angiogenesis [31] — [33].

The mechanisms underlying airway wall remodeling present in the asthmatic lungs, which also involve angiogenesis of the airway wall, are complex and incompletely understood. The observed increased number of micro-vessels present in the airway wall of patients with asthma [26] — [28] , may be explained by the significant higher levels of VEGF and increased HIF expression in the sub-epithelial cell layers of asthma patients relative to healthy controls [14].

It is important to note that high expression of VEGF was reported in the airways of asthma patients [35] , [36]. CM isolated from BSMC cultured under hypoxic conditions demonstrated a significantly increased endothelial sprout outgrowth relative to CM of BSMC grown under normoxic conditions, confirming that BSMC cultured under hypoxic conditions induced the release of pro-angiogenic factors. It has been observed that hypoxia regulates VEGF activities mainly through transcriptional repression of the neuropilin-2 receptor [38].

Furthermore, increased levels of IL-6 and IL-8 have been reported in asthma patients [39]. This suggests that hypoxia may exert differential effects on different cytokines via distinctly different mechanisms. In conclusion, hypoxia has dualistic effect on proliferative and inflammatory responses of both non-asthmatic and asthmatic primary human BSMC.

Our data imply that hypoxia cannot be a direct cause for the observed increased smooth muscle mass in the airway wall of asthma patients. Rather, these cells start to elicit a range of pro-inflammatory cytokines and growth factors that intensify airway wall inflammation and remodeling through advancing the process of neovascularization. A novel strategy to counteract airway wall remodeling may therefore be found in the development of drugs that counteract the process of neovascularization.

Cryosectioning, fixation, staining and photography were performed by Dr Jane Radford with the assistance of Barbara Hernandez in the Histopathology Laboratory, Faculty of Medicine, the University of Sydney. Analyzed the data: LK PB.

Wrote the paper: LK PB. Browse Subject Areas? Click through the PLOS taxonomy to find articles in your field. Abstract Background For oxygen supply, airway wall cells depend on diffusion though the basement membrane, as well as on delivery by micro-vessels. Objective In our study we investigated the effect of hypoxia on proliferation and pro-inflammatory and pro-angiogenic parameter production by human bronchial smooth muscle cells BSMC. Conclusion Hypoxia had dualistic effects on proliferative and inflammatory responses of asthmatic and non-asthmatic BSMC.

Introduction Persistent airway wall remodeling is an important pathology of asthma, which is characterized by basement membrane thickening, increased bronchial smooth muscle mass and neovascularization. Download: PPT. Figure 1.