A journal published by NEJM, turn into a simplified ppt.

1. Presented by Dr. Diptiman Behera, 2nd year PG
Preceptor- Asso. Prof. Dr. Bijan Patnaik
Dept. of General Medicine

2. Asthma and Hypertension are two common chronic
diseases, each with their morbidity, mortality and
economic effects
In this review, we will discuss
• the pathology of asthma,
• the potential mechanistic links between hypertension
and asthma,
• the influence each condition has on the other, and
• approaches to the treatment of hypertension in adult
patients with asthma.

3. HYGIENE HYPOTHESIS
Based on scientific observation that because of lack of exposure to infectious
organisms, the immune system is no longer challenged adequately in children
born in industrialised nations (Schroeder 2008)
In this model, the developing immune system shifts the balance between what
would normally be equal parts of T-helper (Th) cells type 1 and type 2 (Okada
2010) toward a type 2 cell–mediated immunity.
This favors the development of asthma, because Th2 cells produce interleukins
(i.e., IL-4, IL-5, IL-6, and IL-13) that contribute to atopy through immunoglobulin E
production.
Prevalence of asthma are much higher in Western countries

4. Asthma is a syndrome with three cardinal features:
• generalized but reversible airways obstruction;
• bronchial hyper-responsiveness;
• airways inflammation
The general etiologic factors that predispose a person to asthma are atopy and
exposure to environmental triggers.
driver in the differentiation of CD4+ T cells into Th2 cells, and IL-4 also stimulates th
Th2 cells, through the release of IL-5, are associated with eosinophilic inflammation
and, through the release of IL-4 and IL-13, are associated with increased IgE
formation.

6. a is currently understood as a disorder that is characterized by two main endo
Type 2 high inflammation and Type 2 low inflammation.
dominant underlying mechanism, which is largely determined by the T cells or inn
into multiple phenotypes that are distinguished by clinical features, pathologica

8. The Severe Asthma Research Program conducted multiple studies
in which patients with asthma were grouped into discreet clusters
on the basis of variables such as
• clinical characteristics,
• biomarkers,
• lung function,
• cellular profiles,
• atopic status,
• responses to treatment,
• gene expression, and coexisting conditions
It is notable that two studies that included hypertension as a variable showed
cosegregation of hypertension with asthmatic profiles that are typical for the
type 2 low-inflammation endotype.
ge, later onset of asthma, higher body-mass index [BMI], greater severity of disease, and lo

9. Hypertension skews T cells toward a pro-inflammatory type 1 helper T-cell
[Th1 cell] phenotype, characterised by increased interferon-γ responses
and decreased type 2 helper T-cell (Th2 cell) responses.
In such cases, enhanced airway hyperresponsiveness and severe disease are
associated with elevated levels of interferon-γ.
Correspondingly, in hypertension, interferon-γ and Th1-cell polarization
contribute to blood-pressure elevation and its sequelae
flammation in patients with hypertension and asthma reflects the conjoint effect of b

10. Interleukin-17 has also been shown to play a major role in the development of
hypertension and its related end-organ damage
lammatory phenotype in vascular smooth-muscle cells by enhancing the release
• IL-6,
• CXCL8 and CXCL10,
• and C-reactive protein
An elevated level of IL-17 in some patients with severe asthma is correlated with
• neutrophil infiltration,
• airway hyperresponsiveness, and
• lack of sensitivity to glucocorticoids
In these patients, IL-17 induces secretion of pro-inflammatory cytokines from
lung structural cells and airway smooth muscle, such as
• tumor necrosis factor α
• IL-1β
• IL-6
• the chemokines CCL11 (eotaxin) and CXCL8 (IL-8),
which are important in airway inflammation and remodeling

11. Experimental evidence supports the concept that elevated interleukin-6 levels can
drive the differentiation of CD4+ T cells through interaction with transforming growth
factor β to promote skewing toward type 17 helper cells (Th17) cells, leading to a
reduction of regulatory T cells (Tregs)
Regulatory T cells
(Tregs) inhibit both
hypertensive and
asthmatic
inflammation
Type 1– and type 17–biased immune
responses may dually influence both
the expression and the severity of
asthma and hypertensive disease
TGF β
IL-6
Tregs
(—)
Th17CD4+ T cells
Adipocytes
Th1
IFN-γ

13. Predisposing factors
(genetic profile,
stress, and age),
dietary and lifestyle
choices, and
inflammatory
mechanisms all
contribute to the
hypertensive
asthmatic phenotype.
Systemic inflammation
serves as an
underpinning
Smooth-muscle
remodeling, driven in
substantial part by
inflammatory
cytokines, is a critical
component of both
asthma and
hypertension

14. Treatment of Hypertension in Patients with Asthma
Involves control of both conditions, treatment of coexisting conditions,
and the institution of lifestyle modifications
How might the treatment of hypertension affect patients with asthma?
e choice of anti-hypertensive medication appears to be the major determinant of out

15. Beta-Blockers
• Caution in patients of asthma
• not generally recommended as monotherapy for the treatment of hypertension
except in specific cases of congestive heart failure or who have arrhythmias or who
have had myocardial infarction.
Beta-blockers
Nonselective, targeting both the β1
and β2 adrenergic receptors,
relatively cardioselective,
predominantly targeting the β1 receptor
In clinical practice, beta-blockers have been used in patients who had disease that
was stable, who did not have evidence of reduced FEV1, did not increase use of
SABAs, and did not have an increase in symptoms with continued treatment.
A subgroup of patients did have a
decline in FEV1 of 20% or more after
short-term exposure to selective beta-
blockers.
A significant increase in symptoms
and significant decrease in FEV1
was reported only in patients who
received nonselective blockers
SHORT-TERM T/T META-ANALYSIS
Short-acting β2 agonists
(SABAs) action
Completely abolished Blunted

16. Angiotensin-Converting–Enzyme Inhibitors
• ACE inhibitors in patients with asthma and hypertension — are not
contraindicated
Clinical confusion regarding asthma control — ACE inhibitor–related cough
• Incidence of this side effect is unclear, ranging from 2.8 to 40% depending on
ethnicity, genotype, presence of underlying cardiovascular disease,
methodology of assessment, and the specific ACE inhibitor used
• In a case–control trial involving patients with hypertension and asthma, ACE
inhibitors were associated with
• increased asthma morbidity/severity,
• increased use of SABAs,
• increased use of systemic glucocorticoids
Given that ACE inhibitors are considered to be a major drug class for the
treatment of hypertension, clinicians should be alert to the fact that the use of
these drugs can be deleterious in a minority of patients with asthma.

17. Angiotensin-Receptor Blockers
Angiotensin-receptor blockers (ARBs) may be the preferred drugs that act on the
renin–angiotensin system for use in patients with asthma who have hypertension
Inhibition of angiotensin II type 1 receptors has resulted in slight abatement in
bronchial hyper-responsiveness
ARBs appear to target pathways that would address both hypertension and asthma

18. Calcium-Channel Blockers
There are theoretical benefits associated with the use of calcium-channel
blockers in patients with asthma who have hypertension
• decreases smooth-muscle contraction;
• alleviates the bronchoconstriction that may occur in
response to a variety of stimuli
• and induces bronchodilation
In clinical practice, however, calcium-channel blockers have not been shown
to have a salutary effect on asthma outcomes.
Nonetheless, given their physiological profile and efficacy, calcium-channel
blockers are a favoured treatment for patients with asthma who have
hypertension

19. Thiazides
Low-dose thiazides (eg, 12.5 to 25 mg of hydrochlorothiazide once daily) used
alone or in combination with other agents, such as calcium-channel blockers,
are often prescribed for the treatment of hypertension.
In asthma, high doses of a β2 agonist can be associated with hypokalemia,
which appears to be more severe in patients who take diuretics
For a patient with asthma and hypertension who is receiving diuretics as well
as a β2 agonist, the addition of a glucocorticoid or theophylline may
further enhance the risk of hypokalemia.

21. Conclusions
Persons with both hypertension and asthma represent an important subset of the
globally escalating number of persons with cardiovascular and airway disease.
Experimental evidence from studies and observations in human disease highlight
smooth-muscle activation, vascular dysfunction, and systemic inflammation as
unifying characteristics within this cohort.
The influence of type 1 and type 17 inflammatory pathways is noteworthy for
increasing the severity of disease in patients who have hypertension and
severe asthma who are also obese and have metabolic dysfunction
The treatment of patients with both hypertension and asthma should involve an
integrated approach that includes pharmacotherapy and changes in lifestyle
including diet modification, salt restriction, stress reduction, and weight loss

22. Christiansen C. Sandra, M.D., and Zuraw L. Bruce, M.D. Division of
Rheumatology, Allergy, and Immunology, Department of Medicine, University of
California: New Engl J Med 2019;381:1046-57.
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23. THANK
YOU