ward admitted that has frequent exacerbation and sever symptoms

1. 21st of July, 2023
Presenter: Lemi Shiferaw (R1)
Moderator: Dr Selam (Consultant Internist)

2.  Case Discussion
 Introduction
 Epidemiology
 Pathogenesis
 Diagnosis
 Treatment

3. Identification
 Name: Y.M
 Age: 45 years
 Address: A.A
 Occupation: Merchant
 Date of Admission: 29/10/2015
 Date of Discharge: 11/11/2015

4.  HPI:
This is a 45 years old female known asthmatic for the
past 20 years on Salbutamol puff PRN and Prednisolone
10mg po bid for the last 2 years who discontinued the
medication for the past 1 month.
Currently presented with Shortness of breath of 1 week
duration; associated to this, she also has history of
chest tightness.

5.  She was admitted once in this year for asthma
exacerbation
 She has used 5 salbutamol cans in 5 months with night
time awakenings of 2-3 times.
 Otherwise, she has no hx of contact with chronic
coughers, no Hx of other comorbidities like DM, HTN or
Heart disease

6.  G/A: a/s/l
 V/S: BP 100/70, PR: 86, RR: 23, T: 37, SaO2: 80%(atm), 95% on INO2
 HEENT: PCNIS
 LGS: No LAP
 RS: Diffuse wheezing over the post. Chest bilaterally
 CVS: S1/S2 well heard, no M/G
 GIS: Flat and Moves with respiration, No mass or Organomegally
 GUS: No CVAT
 MSS: No Oedema
 IS: No rash
 CNS: COTPP

8. Reticulations at the Right lower lung zone and ipsilateral CPA is blunted
Impression: atypical pneumaonia

10. GINA 2022 Asthma definition:
 Asthma is a heterogeneous disease, usually characterized by chronic
airway inflammation. It is defined by the history of respiratory
symptoms, such as wheeze, shortness of breath, chest tightness and
cough, that vary over time and in intensity, together with variable
expiratory airflow limitation.

11.  Asthma is usually associated with airway
hyperresponsiveness and airway inflammation, but
these are not necessary or sufficient to make the
diagnosis
 In most cases, the airway obstruction is reversible,
but in a subset of asthmatics, a component of the
obstruction may become irreversible
 ’

13. Many clinical phenotypes of asthma have been identified
 Allergic asthma :- associated with a past and/or family
history of allergic disease such as eczema, allergic
rhinitis, or food or drug allergy
 Non-allergic asthma :- The cellular profile of the sputum
of these patients may be neutrophilic, eosinophilic or
contain only a few inflammatory cells (paucigranulocytic).
 Adult-onset (late-onset) asthma -
 Asthma with persistent airflow limitation -
 Asthma with obesity -

14.  Asthma is the most common chronic NCD, affecting over
260 million people globally in 2019
 ∼4.3% prevalence worldwide
 Prevalence continues to increase and is associated with
transition from rural to urban living
 Asthma is more prevalent among children (8.4%) than
adults (7.7%)
 In the US, asthma is more prevalent in blacks than
Caucasians, and black race is associated with greater
case morbidity

16. Conclusion
The rate of uncontrolled asthma in Ethiopia is much
concerning. The most frequently reported predictors for
uncontrolled asthma were; incorrect inhalation
techniques, frequent SABA use, moderate/severe
asthma, comorbid diseases, a history of asthma
exacerbations and irregular follow-up visit. Revising the
asthma management approaches and asthma educations
at each follow-up visit should be strengthened to
minimize the morbidity of uncontrolled asthma.
Moreover, further research with a high-quality design is
required to disclose the category of patients with a high
proportion of uncontrolled asthma.

17.  The pathway to development of asthma can be varied
 There is an interplay between genetic susceptibility and
environmental exposure and endogenous developmental
factors (e.g., aging and menopause)
 These should be distinguished from triggers, which are
environmental factors that worsen asthma in a patient
with established asthma

20. - The patho-biologic processes in the airways that lead to
episodic and chronic airway obstruction of asthma are :-
1. Airway Hyperresponsiveness (AHR)
 AHR is a hallmark of asthma
 It is defined as an acute narrowing response of the
airways in reaction to agents that do not elicit airway
responses in non affected individuals
 Excess narrowing response to inhaled agents as compared
to nonaffected individuals

21. 2. Inflammatory Cells
 Most asthmatics have evidence of chronic inflammation in
the airways.
 Most commonly, this inflammation is eosinophilic in nature.
 In some patients, neutrophilic inflammation may be
predominant, especially in those with more severe asthma.
 Mast cells are also more frequent

22. 3. Airway Smooth Muscle
 Can contribute to asthma in three ways :-
i. It can be hyperresponsive to stimuli
ii. hypertrophy and hyperplasia can lead to airway wall
thickening with consequences for hyperresponsiveness
iii. Airway smooth-muscle cells can produce chemokines and
cytokines that promote airway inflammation and promote the
survival of inflammatory cells, particularly mast cells

23.  Type 2 and Non–Type 2 Inflammation
 Most asthma is accompanied by airway inflammation. In
the past, asthma had been divided into atopic and
nonatopic (or intrinsic) asthma
 The former was identified as relating to allergen
sensitivity and exposure, with production of IgE, and
occurring more commonly in children
 Non atopic was identified as occurring in individuals with
later onset asthma, with or without allergies, but
frequently with eosinophilia

24. Type 2 Inflammation
 Type 2 inflammation is an immune response involving
the innate and adaptive arms of the immune system
to promote barrier immunity on mucosal surfaces
 It is called type 2 because it is associated with the
type 2 subset of CD4+ T-helper cells, which produce
the cytokines interleukin (IL) 4, IL-5, and IL-13

25. Non–Type 2 Processes
 Non–type 2 processes can exist either in
combination with type 2 inflammation or without
type 2 inflammation
 This type of inflammation is more commonly seen in
severe asthma that has not responded to the
common anti-inflammatory therapies.
 In some cases, it may also be associated with
chronic infection, occasionally with atypical
pathogens such as Mycoplasma.

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29.  The diagnosis of asthma is based on the history of
characteristic symptom patterns and evidence of variable
expiratory airflow limitation.
 This should be documented from bronchodilator
reversibility testing or other tests.
 Test before treating, wherever possible, i.e. document
the evidence for the diagnosis of asthma before starting
controller treatment, as it is often more difficult to
confirm the diagnosis afterwards

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31.  In all but the mildest cases, the diagnosis should be
confirmed with pulmonary function testing or
demonstration of airway hyperresponsiveness.
 Studies have shown that more than one-third of patients
with a physician diagnosis of asthma do not meet the
criteria for the diagnosis

32. Pulmonary Function Tests
 PEFR, FEV1, FEV1/FVC – All are
reduced in Asthma
 Reversibility is defined as a ≥12%
increase in the FEV1 and an absolute
increase of ≥200 mL at least 15 min
after administration of a β2-agonist
or after several weeks of
corticosteroid therapy
 Diurnal peak flow variability of >20%
has also been proposed as an indicator
of reversible airways disease

33.  In cases where PFTs are non-confirmatory and the
diagnosis remains in doubt Test to demonstrate
increased reactivity to provocative stimuli in the
laboratory:-
 A provocative dose of Methacholine producing a 20% drop
in FEV1 is calculated, with a value ≤400 μg indicative of
airway reactivity
 Challenge with exercise and/or cold, dry air can be
performed, with a positive response recorded if there is a
≥10% drop in FEV1 from baseline

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35. Eosinophil Counts
 A large proportion of asthma patients not treated with
oral or high-dose ICSs will have eosinophil counts ≥300
cells/μL
 Eosinophil counts correlate with severity of disease in
population studies.
 Their presence in patients with severe asthma indicates a
likelihood that the patient would respond to medications
targeted at type 2 inflammation.

36. IgE, Skin Tests, and Radioallergosorbent Tests
 Total serum IgE levels are useful in considering whether
patients with severe asthma would be eligible for anti-IgE
therapy
 Levels >1000 IU/mL should prompt consideration of ABPA
 Skin tests, or their in vitro counterparts that detect IgE
directed at specific antigens (RAST), can be useful in
confirming atopy and suggesting allergic rhinitis, which can
complicate asthma management

37. Exhaled Nitric Oxide
 Fraction of exhaled NO (FeNO) in exhaled breath is an
approximate indicator of eosinophilic inflammation in the
airways
 It’s easily suppressed by ICSs & thus, can be used to assess
adherence in patients in whom it was initially elevated
 Elevated levels (>35–40 parts/billion) in untreated patients
are indicative of eosinophilic inflammation.
 Levels >20–25 ppb in patients with severe asthma on
moderate- to high-dose ICS indicate either poor adherence
or persistent type 2 inflammation despite therapy

38. Uncontrolled asthma includes one or both of the following :
 Poor symptom control (frequent symptoms or reliever use,
activity limited by asthma, night waking due to asthma)
 Frequent exacerbations (≥2/year) requiring OCS, or serious
exacerbations (≥1/year) requiring hospitalization

39. Difficult-to-treat asthma
 Is asthma that is uncontrolled despite prescribing of
medium or high dose ICS with a second controller (usually
a LABA) or with maintenance OCS OR
 Asthma that requires high dose treatment to maintain
good symptom control and reduce the risk of
exacerbations

40. Severe asthma
 Subset of difficult-to-treat asthma
 It means asthma that is uncontrolled despite adherence
with maximal optimized high dose ICS-LABA treatment and
management of contributory factors OR
 That worsens when high dose treatment is decreased
 Therefore, ‘severe asthma’ is a retrospective label

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42.  1. Confirm the diagnosis (r/o differential diagnoses)
 2. Look for factors contributing to symptoms and
exacerbations e.g. Incorrect inhaler technique (-80%),
Suboptimal adherence, Comorbidities (GERD, COPD,
OSA, bronchiectasis, cardiac disease, and kyphosis due
to osteoporosis), Modifiable risk factors and triggers,
Regular or over-use of SABAs, Anxiety, depression and
social and economic problems, Medication side-effects

43. 3. Review and optimize management
 Provide asthma self-management education
 Confirm that the inhaler is suitable for the patient
4. Review response after 3-6 months, Review:
 Symptom control (frequency, SABA use, night time waking,
activity limitation), Exacerbations since previous visit, and
how they were managed
 Medication side-effects, Inhaler technique & adherence
 Lung function, Patient satisfaction and concerns

44.  YES: if asthma is still uncontrolled, the diagnosis of severe
asthma has been confirmed
 NO: if asthma is now well controlled, consider stepping
down treatment – begin from OCS then remove other add-
on therapy, then decrease ICS dose, but do not stop ICS

45. 5. Assess Asthma phenotype ( T2 vs NT2)
 Type 2 inflammation is found in the majority of people with
severe asthma
 Type 2 inflammation is often characterized by elevated
eosinophils or increased FeNO & may be accompanied by
atopy

46. Additional evaluations for comorbidities may be necessary
 Esophageal studies in those who have symptoms of reflux
 In patients with nonreversible disease, obtain α1AT level
 Chest CT can be useful to assess for the presence of
bronchiectasis and other structural abnormalities that
could produce airway obstruction
 Induced sputum may be used in more specialized centers to
help characterize type 2 and non–type 2 inflammation by
detection of eosinophils and neutrophils, respectively

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49.  For safety, GINA no longer recommends SABA-only treatment
for Step 1 in adults and adolescents
 GINA now recommends that all adults and adolescents with
asthma should receive ICS-containing controller treatment, to
reduce the risk of serious exacerbations
 Regular use of SABA, even for 1–2 weeks, is associated with
adverse effects:
◦ B-receptor downregulation, decreased bronchoprotection, rebound
hyperresponsiveness, decreased bronchodilator response, increased allergic
response, and increased eosinophilic airway inflammation

50.  Dispensing of ≥3 canisters per year (i.e. daily use) is
associated with higher risk of severe exacerbations
 Dispensing of ≥12 canisters per year is associated with much
higher risk of death
 GINA Rx figure now shows two ‘tracks’, based on evidence
about outcomes with the two reliever choices across asthma
severity
 Track 1, with low dose ICS-formoterol as the reliever, is
the preferred approach
 Track 2, with SABA as the reliever, is an alternative

51.  Low dose ICS-formoterol as reliever reduces the risk of
severe exacerbations --- preferred!
 Patient use low dose ICS-formoterol in a single inhaler for
symptom relief
 In Steps 3–5, patients also take ICS-formoterol as their
daily controller treatment. Together, this is called
‘maintenance and reliever therapy’ or ‘MART’
 ICS-formoterol ICS-LABA not be used as the reliever in
patients prescribed a different for their controller
therapy

52.  Alternative if Track 1 is not possible or is not preferred by a
patient with no exacerbations on their current therapy
 In Step 1, the patient takes a SABA and a low dose ICS
together for symptom relief when symptoms occur, in a
combination inhaler, or with the ICS taken right after the SABA
 In Steps 2–5, the patient takes ICS-containing controller
medication regularly every day & uses SABA for symptom relief.

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58.  GINA does not distinguish between ‘intermittent’ and ‘mild
persistent’ Patients with so-called ‘intermittent’ asthma are still
at risk of severe exacerbations
 No evidence about initiating MART in Step 5 in patients receiving
add-on treatment such as LAMA or biologic therapy
 But if a patient is already taking MART, switching them to
conventional ICS-LABA plus as-needed SABA may increase the
risk of exacerbations

59.  Step 5 recommendations for add-on LAMA have been
expanded to include combination ICS-LABA-LAMA, if
asthma is persistently uncontrolled despite ICS-LABA
 Add-on tiotropium in separate inhaler (ages ≥6 years)
 Triple combinations (ages ≥ 18yr): beclometasone
formoterol-glycopyrronium; fluticasone furoate-vilanterol-
umeclidinium; mometasone-indacaterol-glycopyrronium

60. Lung function:-
 Adding LAMA to medium or high dose ICS-LABA modestly
improves lung function (Evidence A) but not symptoms
Severe exacerbations
 In some studies, add-on LAMA modestly increased the time
to severe exacerbation requiring OCS (Evidence B)
 For exacerbations, it’s important to ensure that the patient
receives sufficient ICS, i.e. at least medium dose ICS-
LABA, before considering adding a LAMA

61. Add-on azithromycin
 Add-on azithromycin three days a week has been confirmed
as an option for consideration after specialist referral
 - Significantly reduces exacerbations in patients taking
high dose ICS-LABA
 - Significantly reduces exacerbations in patients with
eosinophilic or non-eosinophilic asthma
 - No specific evidence published for azithromycin in
patients taking medium dose ICS-LABA

62. Before considering add-on azithromycin
 Check sputum for atypical mycobacteria
 Check ECG for long QTc (and re-check after a month of
treatment)
 Consider the risk of increasing antimicrobial resistance
(population or personal)

63.  When assessing eligibility, repeat blood eosinophils if low
at first assessment
 One study found that 65% patients on medium or high dose
ICS-LABA shifted their eosinophil category during 12
months’ follow-up
 Additional indications for these therapies in Europe and/or
USA have been listed:

64.  Omalizumab: chronic idiopathic urticaria, nasal
polyposis
 Mepolizumab: hypereosinophilic syndrome,
eosinophilic granulomatosis with polyangiitis (EGPA)
 Benralizumab: no additional indications at present
 Dupilumab: chronic rhinosinusitis with nasal
polyposis (CRSwNP)

65.  Asthma-COPD overlap’ and ‘asthma +COPD’ are terms
used to collectively describe patients who have
persistent airflow limitation together with clinical
features that are consistent with both asthma and
COPD
 In epidemiological studies, reported prevalence rates
for asthma-COPD overlap have ranged between 9%
and 55% of those with either diagnosis.

66.  Smoking can blunt the response to ICS.
 Further, it has been difficult to demonstrate the
effectiveness of biologic agents targeted at type 2
inflammation in patients with COPD despite the
presence of ≥300 circulating eosinophils/μL.
 Additionally, in patients with both diseases, earlier
initiation of anticholinergics may be considered.

67.  Lung function testing is essential to confirm the
following
 The presence of persistent expiratory airflow limitation
 Variable expiratory airflow limitation
 Spirometry can confirm both persistent airflow
limitation and reversibility
 PEF may help to confirm reversible airflow limitation
and the diagnosis of asthma by demonstrating excessive
variability
 PEF is not as reliable as spirometry, and a normal PEF
does not rule out either asthma or COPD

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69.  Harrison Principles of Internal Medicine
 Uptodate 2023
 Fishman’s Pulmonary Disease and Disorders
 GINA Guideline, 2023

70. THANK
YOU!