2. Frances M. Rackemann 1887-1973:
In 1947,he classified asthma into
atopic or nonatopic
based on the presence or absence
of clinical symptoms precipitated by
one or more common aeroallergens,
supported by skin prick test
F. M. Rackemann, The American Journal
of Medicine, vol. 3, no. 5, pp. 601–606,
3. Recent results led to the conclusion that both
kinds of asthma share more similarities than
differences .
•R. Pawankar et al. ,Allergy Frontiers: Clinical Manifestations, 321,2009
4. further studies has promoted the concept that asthma
consists of multiple phenotypes, each of which is defined
by distinct clinical, functional and pathobiological patterns.
Mouthuy J, et al. Am J Respir Crit
Care Med. 2011 .
5. NON-ATOPIC ASTHMA
there have been major advances in our
understanding of the molecular mechanisms of
atopic asthma, but relatively little progress in
understanding of non-atopic asthma.
Recently, scientific evidence has challenged the
dualistic concept of extrinsic and intrinsic asthma
Siroux, V. et al. Eur. Respir. J. 38, 310–317 (2011).
6. NON ATOPIC ASTHMA IS
TYPICALLY:
late-onset .
More common in females
Tends to be more severe .
Requiring higher doses of corticosteroids .
Often starts following respiratory tract infection.
Less familial association
http://thorax.bmj.com/ on April 6, 2016
8. COMMON TRIGGERS IN BOTH ATOPIC & NON
ATOPIC ASTHMA,
Barnes PJ,Exp Allergy. 2009 Aug;39(8):1145–51.
9. Mouthuy J, et al. Am J Respir
Crit Care Med. 2011 .
Immunopathological mechanisms in non-
atopic asthma.
10. CHALLENGES TO THE DUALISTIC CONCEPT
OF ATOPIC AND NON ATOPIC ASTHMA.
Inflammatory cytokines IL-4, IL-5, and IL-13 in bronchial
biopsies were similar both in allergic and in intrinsic
asthmatics.
enhanced expression of high-affinity IgE receptor (Fc RI)ɛ
in bronchial biopsies obtained from non-atopic
asthmatics is probably due to IgE synthesis occurring at
least locally in the airways of these patients, despite
their having negative skin prick tests and low serum IgE.
Pillai P, et al. ISRN Allergy. 2011
13. PROBABLE IMMUNOPATHOGENESIS:
• Autoimmunity theory:
IgE could express a humoral autoimmunity, against
human proteins with structural similarity to allergens .
in accordance with the late-onset occurrence of intrinsic
asthma, seen mainly in females. Anti-nuclear antibodies
are more common in patients with asthma than non-
asthmatics,
Autoantibodies to cytokeratin-18 have been described in
patients with non atopic asthma
14. SUPERANTIGEN THEORY
invasion of airway epithelial cells by S. aureus causes
the release of staphylococcal superantigens which act
on airway B lymphocytes to cause local production of
polyclonal IgE, together with IgE directed against
staphylococcal antigens .
This leads to sensitization of mast cells, which can be
activated by the usual asthma triggers ,
also stimulate clonal expansion of T-cells, resulting in
increased Th2 cells and CD8+
cells while suppressing
regulatory T cells
Jing L.etal.,Allergy Asthma Immunol Res. 2014 May; 6(3): 263–266.
15. • The monomeric IgE theory
• Is IgE an independent sensitizer of effector
cells (mast cells and basophils) triggering
bronchial hyperresponsiveness even in the
absence of specific sensitizations in non-
allergic patients.
• Several in vitro studies have supported
this idea showing that bronchial
hyperresponsiveness in tracheal segments
may occur after incubation with sera of
patients with high IgE levels .
Kashiwakura J .Adv Exp Med Biol. 2011;716:29-46.
16. IN CONCLUSION:
Atopic and non atopic asthma share more similarities
than differences .
Local IgE, cytokine production and bronchial
epithelial components ,more or less the same
family history is strongly associated with non atopic
asthma as well.
Despite the absence of circulating peripheral IgE in
non-atopic asthmatics there is activation of the
cellular machinery of atopy at least locally in the
bronchial mucosa
17. Omalizumab may be tried in non-allergic asthmatics
As superantigens may be involved in the pathogenesis of
non atopic asthma,so measures to eradicate
microorganisms might be effective.
Intravenous immunoglobulin (IVIG), which has been used in
the treatment of toxic shock syndrome associated with
staphylococcal toxins ,may be beneficial in treating asthma.
Since autoantibodies to epithelial proteins have been
reported, the use of immunosuppressants may be indicated
More studies are needed to clarify further phenotypes and
endotypes of non atopic asthma