I am professionally pharmacist. These slides for pharmacy department students based on clinical subject. Very helpful for students who get more benefits.

1. Pulmonary unit
ASTHMA (Acute/Chronic)
https://www.aafp.org/afp/2011/0701/p40.html
Koda Kimble
Davidson (for diagnosis)
Dipiro(for treatment)

2. Introduction
Chronic inflammatory disorder of the airways.
– Wheezing, breathlessness, chest tightness, and cough.
– Particularly at night & in the early morning.
– Airflow obstruction is often reversible.
■ Co-existing symptoms of Fever,LOA, LOW,Ankle
swelling,Palpitations.
• Aspirin can cause asthma through the production of
cysteinyl leukotrienes.
• Cells that play a role are:
– Mast cells.
– Eosinophils,
– T lymphocytes.
– Neutrophils.
– Epithelial cells.
1997 NIH guidelines

3. Etiology
Childhood-onset
asthma
Associated with atopy.
Genetic predisposition for the development of immunoglobulin
E (IgE)-mediated response to common aeroallergens.
positive family history of asthma and allergy to tree and grass pollen, house
dust mites, household pets, and molds.
Adult-onset
asthma
Many adults with asthma have a negative family history and
negative skin tests.
Patients may have nasal polyps, aspirin sensitivity, and sinusitis.
Exposure to factors (e.g.,wood dusts, chemicals) at the workplace.
factors include viral infections,diet, exposure to tobacco smoke, and
environmental pollutants.

4. Pathophysiology

6. Pathophysiology
Inflammatory
cells and
mediators.
Mast cells, eosinophils, T lymphocytes, neutrophils,epithelial
Cells.
Bronchial epithelium in asthmatics is fragile, with various abnormalities
including destruction of ciliated cells.
After exposure to an asthma-precipitating factor (e.g., aeroallergen),
inflammatory mediators are released from bronchial mast cells, macrophages,
T lymphocytes, and epithelial cells.
These mediators causes activation of other inflammatory cells, most notably
eosinophils.
Eosinophils cause airway injury, including epithelial damage, mucus
hypersecretion, and increased reactivity of smooth muscle
Cytokines (e.g.,
interleukin [IL]-4
and IL-5)
TH2 lymphocytes release cytokines.
at least 27 cytokines may have a role in the pathophysiology of asthma.
Exhaled nitric
oxide (NO),
biomarker of airway inflammation.
Bronchial NO has been found to be elevated during periods of exacerbations.
decreased with administration of inhaled steroids but not β2-agonists.
Airway
remodeling
refers to structural changes, including an alteration in the amount and
composition of the extracellular matrix leading to airflow obstruction.
long-term airway inflammation in asthma may result in airway remodeling

8. Hyper-reactivity defined as an exaggerated response of bronchial smooth muscles to trigger
stimuli
Examples of these stimuli include inhaled allergens, respiratory viral infection,
cold, dry air, smoke, other pollutants.
Endogenous Stimuli includes poorly controlled rhinitis, sinusitis, and
gastroesophageal reflux disease.
Premenstrual asthma has been reported, but the exact hormonal
mechanism is not known.
Characterized by periods of remissions and exacerbations.
Inflammation appears to be the primary process in the pathogenesis of
bronchial hyperreactivity
Symptoms of Asthma
Clinical
presentation.
intermittent episodes of expiratory wheezing, coughing, and
dyspnea.
chest tightness or a chronic cough that is not associated with wheezing.
Symptoms may be precipitated by:
● Exercise. ● Cold weather. ● Allergen exposure (e.g. pets, occupational).
● Viral respiratory tract infections. ● Drugs (β-blockers, aspirin and NSAIDs).

9. Breathlessness
■ Most common symptom.
■ Severity?
■ Walk how far?
■ Climb stairs how many flights?
■ Effect on his job, social activity?
■ Timing of breathlessness?
Cough
■ Duration
■ When
■ Persistent or intermittent
■ Pain?
■ Dry or wet

10. Classifications of Severity of an Asthma Exacerbation
DEGREE OF
SEVERITY
SYMPTOMS
AND SIGNS
INITIAL
PEF (OR
FEV1
)
CLINICAL COURSE
Mild Dyspnea only with
activity
PEF ≥ 70
percent
Usually treated at home.
Prompt relief with inhaled short-acting beta2
agonist
Possible short course of oral systemic corticosteroids.
Moderate Dyspnea interferes
with or limits usual
activity
PEF 40 to
69 percent
Usually requires office or emergency department
visit.
Relief from frequent inhaled short-acting
beta2
agonist
Oral systemic corticosteroids; some symptoms last
for one to two days after treatment begins
Severe Dyspnea at rest;
interferes with
conversation
PEF < 40
percent
Usually requires emergency department visit and
likely hospitalization.
Partial relief from frequent inhaled short-acting
beta2
agonist
Oral systemic corticosteroids; some symptoms last
for more than three days after treatment begins
Adjunctive therapies are helpful
life threatening Too dyspneic to
speak; perspiration
PEF < 25
percent
Requires emergency department visit/hospitalization;
possible intensive care unit.
Minimal or no relief from frequent inhaled
short-acting beta2
agonist & Intravenous
corticosteroids

11. Physical examinations
■ General appearance
■ Cyanosis
■ Finger clubbing
■ Head and neck
■ Chest inspection
■ Chest palpation

12. Full systemic enquiry
■ Past medical history
■ Family history
■ Social history
■ Current medications
■ Allergies

13. Diagnosis and Monitoring
History Detailed history of symptoms of wheezing, chest tightness,
shortness of breath, and coughing.
Episodes may worsen seasonally.
History of nocturnal symptoms with awakening in the early morning is a
critical component to assess.
History of symptoms after exposure to other common triggers (e.g., cats,
perfume, second-hand tobacco smoke).
A positive family history, presence of rhinitis or atopic dermatitis also are
significant.
Skin testing Useful in identifying triggering allergens.
Pulmonary
Function Tests
SPIROMETRY:
Performed when clinically stable.
Lung volumes often are measured to obtain information about the size of the patient’s
lungs.. lung volumes depend on age, race, gender, height,weight.
can affect the volume of air that can be inhaled and exhaled.
Tidal volume: volume of air inspired or expired during normal breathing.
Vital capacity (VC): volume of air blown off after maximal inspiration to full
expiration. Patients with obstructive lung disease have a decreased VC.
Residual volume (RV):volume of air left in the lung after maximal expiration.
Patients with obstructive lung disease have increased RV.
Functional residual capacity (FRC):volume of air left after a normal expiration.
Patients with obstructive lung disease have a normal TLC.
Total lung capacity (TLC): VC plus the RV.

14. Spirometer Used to evaluate the performance of the patient’s lungs, thorax, and respiratory
muscles in moving air into and out of the lungs.
FEV.
Measured by having the patient exhale into the spirometer as forcefully and as
possible after maximal inspiration.
The resulting volume curve is plotted against time so that expiratory flow can be
estimated.
FEV1 Gas exchanged in one second by a forced expiration.
The FEV1 usually is expressed as a percentage of the total volume of air
exhaled and is reported as the FEV1 to FVC ratio.
Healthy persons generally can exhale at least 75% to 80% of their VC
in 1 second.
PEAK EXPIRATORY
FLOW
Maximal flow that can be produced during the forced expiration.
A healthy, average sized young adult male typically has a PEF of 550 to 700
L/minute.
Blood Gas
Measurements
ABGs (i.e., PaO2, PaCO2, and pH).
ABG measurements also are dependent on the patient’s cardiovascular
Status.
Another measure oxygen saturation is the ratio between the actual amount of
oxygen bound to hemoglobin and the potential amount of oxygen that could be
bound to hemoglobin at a given pressure.

16. Guidelines
• National Institutes of Health, National Heart, Lung,
and Blood Institute. National Asthma Education and
Prevention Program. Full Report of the Expert
Panel: Guidelines for the Diagnosis and
Management of Asthma
(EPR-http://www.nhlbi.nih.gov/guidelines/asthma.
• British guideline on the management of
asthma

17. Immediate assessment of acute severe asthma
Acute severe asthma PEF 33–50% predicted (< 200 L/min)
Inability to complete sentences in 1 breath
Heart rate ≥ 110/min
Respiratory rate ≥ 25/min
Life-threatening
features
PEF < 33% predicted (< 100 L/min)
SpO2 < 92% or PaO2 < 8 kPa (60 mmHg)
Normal or raised PaCO2
Silent chest/feeble respiratory effort
Cyanosis
Hypotension
Exhaustion
Confusion
Coma
Bradycardia or arrhythmias
Near-fatal asthma ↑PaCO2 and/or requiring mechanical ventilation with raised
inflation pressures

18. Asthma Control Test

19. Sample Questionsa for the Diagnosis and
Initial Assessment of Asthma

20. Obstructive versus Restrictive
Airway Disease
restrictive disease obstructive disease
limits airflow during inspiration,
results from a loss of elasticity (e.g., fibrosis,
pneumonia) or physical deformities of the chest
(e.g., kyphoscoliosis).
limit lung expansion.
limits airflow during expiration.
Narrow air passages, create air turbulence, and
increase resistance to airflow.
Expiratory flow is depressed.

21. Goals of Therapy
Reduce
Impairment
Prevent chronic/troublesome symptoms.
maintain “normal” pulmonary function.
require infrequent use of SABA.
meet patients’ and families’ expectations of and satisfaction.
Reduce Risk: Prevent recurrent exacerbations of asthma.
minimize the need for ED visits/hospitalizations.
Prevent progressive loss of lung function.
Provide optimal pharmacotherapy with minimal or no adverse effects.
Long-Term Management
Measures of asthma assessment and monitoring.
Education for a partnership in asthma care.
Control of environmental factors/comorbid conditions that affect asthma.
Medications.

22. TREATMENT/Aerosol
• The drug is either in solution or a suspended micronized powder.
• Inhalation of SABA provides rapid bronchodilation.
• Inhaled corticosteroids (ICSs) enhance lung activity.
• Specific agents (cromolyn, formoterol, salmeterol,ipratropium
bromide) are only effective by inhalation.
Device Determinants of Delivery
Jet nebulizers nebulizers can deliver 2% to 15% of the actuated dose
Ultrasonic nebulizers
metereddose
inhalers (MDIs)
MDIs can deliver 15% to 50% of the actuated dose.
dry powder inhalers
(DPIs)
DPIs can deliver 10% to 30%of the actuated dose.
TABLE 15-4 Factors Determining Lung Deposition of Aerosols(DIPIRO)S.
Instructions for inhaler use:
http://www.nhlbi.nih.gov/guidelines/archives/epr-2/index.htm.

23. Drugs Used in Acute Asthma
β2-
Agonists
SABA
Page
(912-913
Dipiro)
SABA..most effective .
1st choice…management of ASA.
Frequent administration every 20 min
or continuous neb.
continuous neb recommended for
patients having an unsatisfactory
response.
Dose for children often is listed on a
weight basis.
Adults have fixed maximal doses.
clinical trials..
equal/greater efficacy/greater safety of
aerosolized β2- agonists .
Systemic adverse effects…systemic
β2-agonist therapy.
Children younger than 2 yrs…significant
responses from neb albuterol.
mechanical ventilator circuits
(infants, children, and adults in respiratory
failure).
Continuous vs intermittent (hourly) neb
albuterol.
Cortico-
steroids
(Page 913
Dipiro)
Systemic corticosteroids indicated in all
patients with AA.
Therapy continued until hospital
discharge.
Tapering the IV cs dose for outpatient
therapy.
3- to 10-day courses of oral
prednisone…..effective.
High-dose.. higher side effects
IV therapy..no advantage over oral
administration.
patients achieve normal FEV1 within 48
hours.
maintaining IV cs for 10-14 days may be
unnecessarily.
Multiple daily dosing of systemic
corticosteroids VS OD.

24. Anticholinergics
Page 914 Dipiro.
Inhaled ipratropium bromide.
multiple-dose.. Initial therapy
reduces hospitalization rate.
ipratropium bromide in the eyes
may produce pupillary dilation.
Use tight mask or mouthpiece
Ipratropium bromide poorly absorbed
and produces minimal/no systemic
effects.
administering ipratropium bromide by
nebulizer…Care should be taken.
Ipratropium bromide is not a
vasodilator unlike β2-agonists.
Alternative
Therapies
Page 914 Dipiro
Aminophylline:
increase the risk of ADR
ED use of aminophylline.. not been
Recommended.
does not enhance improvement in lung
function.
Magnesium sulfate:
potent bronchodilator.
relaxation of smooth muscle.
CNS depression.
IV magnesium sulfate use in ED is
controversial.
Helium
given as a mixture of helium and
O2 (heliox)
can lower resistance to gas flow.
increase ventilation.
Others inhalational anesthetics.
volatile anesthetics…not recommended
Ketamine…. recommended

25. Drug Class Information/Acute Asthma
SABA
TABLE 15-8
Page 917
Dipiro
Effective bronchodilators.
as-needed treatment of intermittent episodes of bronchospasm.
produces smooth muscle relaxation, mast cell membrane stabilization, and skeletal
muscle stimulation.
Enhances insulin secretion,decrease in serum K concentration.
β1-receptor stimulation produces excessive cardiac stimulation(cardiac
arrhythmias).
Catecholamines have a shorter duration of action.
Aerosol administration of the SABA provides more rapid response.
intensity and duration of response are dose dependent.
Chronic administration of β2-agonists leads to downregulation.
Systemic
Cortico-
steroids
Table 15-9
Page 918
Dipiro
Most effective anti-inflammatories.
1 to 2 weeks -----1 to 2 mg/kg/day of prednisone.
reduces mucus production and airway edema.
4 to 12 hours may be required before any clinical response is noted.
Chronic use of corticosteroids does not induce corticosteroid
Dependence.
Effects and side effects are dose and duration dependent.
short bursts (≤10 days)…corticosteroid side effects occur.

26. Anticholinergics do not have an FDA-labeled indication for asthma.
competitive inhibitors of muscarinic receptors.
they reverse cholinergic-mediated bronchoconstriction.
Ipratropium bromide, Tiotropium bromide,,
not as effective as β2-agonists.
intensity and duration of action are dose dependent.
Ipratropium bromide is only indicated as adjunctive therapy in acute severe
asthma
EVALUATION OF THERAPEUTIC OUTCOMES(Figures 15-6 and 15-7 Page 922 Dipiro)
Frequency of monitoring depends on the severity of the exacerbation.
Lung function(spirometric or peak flow measurements-5 to 10 minutes after each
Treatment)
O2 saturations
Patients not achieving an initial response should be monitored every 0.5 to 1 hour.
decision to admit to the hospital should be made within 4 to 6 hours of entry to the ED.
duration of hospitalization following admission is 2 to 3 days.

27. TREATMENT/Acute Severe Asthma
primary goal….
prevention of life-threatening asthma,Correction of significant hypoxemia,Rapid reversal of
airflow obstruction,Reduction of the likelihood of relapse.
Development of a written asthma action plan in case of a further exacerbation.
Goals are best achieved by early initiation of treatment and close monitoring of objective
measures.
Physical examination should be obtained while initial therapy is being provided.
Predictor of
outcome
Improvement in FEV1 at 30 minutes following inhaled β2-agonists.
O2
supplementation
To maintain O2 saturations above 90% (0.90) (or >95% [0.95] in pregnant women and
those who have coexistent heart disease.
Pharmacologic
Treatment
short-acting inhaled β2-agonists (SABA)
depending on the severity, systemic corticosteroids, inhaled ipratropium, and O2.
(Figs. 15-6 and 15-7).
Risk factors history of previous severe asthma exacerbations.
Comorbidities.
use of more than two canisters per month of short-acting inhaled β2-agonists.
current intake of oral corticosteroids.
TABLE 15-6 Dosages of Drugs of Acute Severe Exacerbations of Asthma in the Emergency Department or Hospital (Dipiro)

28. Home Management/ Acute Asthma

29. Hospital
Management
FIGURE 15-7(Asthma/Dipiro)

30. Cont/Acute Asthma
Investigation
Complete blood count(if fever or purulent sputum),Modest leukocytosis common in asthma.
Chest radiography not recommended for routine assessment.
Serum electrolytes (potassium, magnesium, and phosphate)should be monitored if high-dose continuous inhaled or systemic
β2-agonists are to be used/in patients who take diuretics regularly/in patients with cardiovascular disease.
can produce transient decreases in potassium, magnesium, and phosphate.
excessive elevations of glucose and lactic acid may result from combination of high-dose β2-agonists & systemic
corticosteroids.
Response
to
Therapy.
Should be significant improvement within the first 30 to 60 minutes of therapy.
In Hospitalized patients 20% improvement is seen within the first 2 hours.
Hypoxemia is correctable by low-flow O2.
reversal of lung function may take 12 to 24 hours.
complete restoration takes up to 3 to 7 days.
Counseling
points
Provide the patient with a written self-management action plan.
Should be taught how to use a peak flow meter and monitor morning peak flows at home.
Signs of severe obstruction in children are increased RR, increased HR,inability to speak more than 1 or 2
words between breaths.
O2 saturations should be measured in all patients not responding to initial therapy.
On admission, the peak flows or clinical symptoms should be monitored every 2 to 4 hours.
Prior to discharge from the ED or hospital, the patient should be given a sufficient supply of prednisone,
taught purpose of the medications,proper inhaler technique.
referred to followup asthma care within 1 to 4 weeks.
Key to
Successful
Treatment
Early recognition of deterioration/Easy access by telephone to healthcare providers.
aggressive treatment/availability of oral prednisone to begin at home/
patient and/or parent education. teaching self management skills/written action plans/

31. Treatment/Chronic Asthma
Diagnosis challenge testing with exercise, histamine, methacholine, or mannitol can be used.
Serum IgE and sputum and blood eosinophil determinations.
Very high peripheral blood eosinophil counts ……allergic bronchopulmonaryaspergillosis.
Skin testing for identifying triggers.
Hyperinflation… chest roentgenogram.
Pharmacologic
Therapy
(Table 15-12)
Page 927
Dipiro
ICSs are considered the preferred long-term control therapy for persistent asthma.
Low- to medium-dose ICSs improve lung function, and reduce severe exacerbations.
more effective than cromolyn, theophylline.
reduces the risk of dying from asthma.
safe for long-term administration.
Dose (TABLE 15-12 page 928 Dipiro)
ICS and LABA:
For those patients inadequately controlled on low-dose ICSs.
either an increased dose of the ICS.
Or combination of ICS and LABA.
Alternatives could be theophylline to ICSs.
combination of ICS/LABA more effective than doubling ICS dose.
high doses ICSs plus LABA reserved for patients with
severe persistent asthma

32. Drug Class Information/Chronic Asthma
Inhaled
Corticosteroids
Details
(Table 15-13)
Page 931
Dipiro
high topical potency to reduce inflammation.
Low systemic activity.
Different devices may result in twofold differences in delivery.
delivery method make a significant difference.
beclomethasone dipropionate, budesonide, ciclesonide, flunisolide, fluticasone
propionate, and mometasone furoate.
systemic clearance of the available ICSs is very rapid.
all undergo extensive first-pass metabolism.
Mouth rinsing and spitting will also reduce the oral availability
ICSs produce dose-dependent systemic effects.
Symptoms improve in the first 1 to 2 weeks of therapy.
will reach maximum improvement in 4 to 8 weeks.
ADR from ICSs include oropharyngeal candidiasis and dysphonia that are dose
dependent.
spacer device with MDIs can decrease oropharyngeal deposition.
twice-daily dosing of most ICSs.
Milder asthma, once-daily dosing is often sufficient
Long-Acting
Inhaled
β2-Agonists
LABA
(Page 933 Dipiro)
LABAs are recommended for chronic therapy only in combination with
ICSs (formoterol and salmeterol)
provide long-lasting bronchodilation.
LABAs has not yet been approved for asthma.
LABAs will produce dose-dependent systemic β2-agonist effects.
formoterol has a more rapid onset of action.
LABAs should not be used as monotherapy for asthma.

33. Contd-LAB
A
in children 12 years and older…. LABAs are preferred adjunctive therapy to ICSs.
Combination treatment with ICS/LABA provides greater asthma control.
LABAs should not be used as monotherapy for asthma.
an increased risk for severe, life-threatening exacerbations
and asthma-related death with LABA monotherapy.
tolerance is produced with chronic administration of LABAs.
Methyl-xa
nthines
high risk of severe life-threatening toxicity and numerous drug interactions.
Theophylline…moderately potent bronchodilator with mild anti-inflammatory properties.
Sustained release product is the preferred oral preparation.
Toxicities include nausea, vomiting, tachycardia, jitteriness, and difficulty sleeping ,cardiac
tachyarrythmias and seizures.
Routine monitoring of serum concentrations is essential for the safe and effective use.
Theophylline clearance is age dependent.
The addition of theophylline to ICSs is similar to doubling the dose of the ICS.
overall less effective than the LABAs as adjunctive therapy
Cromolyn
Na
mast cell stabilizer and inhibits/only effective by inhalation,
inhibits neurally mediated bronchoconstriction, it does not have bronchodilatory effect.
intensity and duration of protection against various challenges are dose dependent.
Cromolyn is no more or less effective than theophylline.
not as effective as the ICSs for controlling persistent asthma.
patients will experience an improvement in 1 to 2 weeks.
initially should receive cromolyn four times daily, and then only after
stabilization of symptoms may the frequency be reduced to three times daily.

35. Leukotriene
Modifiers
zafirlukast and montelukast, zileuton.
they reduce allergen-, exercise-, cold-air hyperventilation–, irritant-, and aspirin-induced
asthma.
not preferred alternatives in mild persistent asthma nor as alternative add-on therapy for
moderate persistent asthma.
improve pulmonary function tests, decrease nocturnal awakenings
and β2-agonist use, and improve asthma symptoms.
Effective orally, and can be administered once or twice a day.
less effective in asthma than low doses of ICSs.
not as effective as LABAs when added to ICSs for moderate
persistent asthma.
there is some evidence that patients with aspirin-sensitive asthma do well.
also have modest efficacy in allergic rhinitis.
idiosyncratic syndrome has been reported in a small number of patients treated with
zafirlukast and montelukast.
Anti-IgE
Omalizumab
Page 938
Dipiro.
recombinant anti-IgE antibody.
for the treatment of allergic asthma
administered subcutaneously.
Doses range from 150 to 375 mg and are given at either 2- or 4-week intervals.
approved for patients greater than 12 years.
Other options Miscellaneous Therapies (Immunomodulators)
Future Therapies.