CPP LECTURE PRELIMS

Asthma

A complex disorder and has been defined as “a heterogeneous disease, usually characterized by chronic airway inflammation.”

Airflow limitation

results in wheezing, breathlessness, chest tightness, and coughing, particularly at night or early in the morning

Pathogenesis of Asthma

headache

stuffy runny nose

sore throat

coughing or wheezing

difficulty sleeping

feeling moody or irritable

tiredness or weakness during physical activity

Warning signs of an Asthma (Clinical Presentations)

chest tightness

coughing especially at night or when laughing

difficulty breathing

shortness of breath

sleep problems resulting from breathing issues

a wheezing or whistling sound in the chest when exhaling

Symptoms of Asthma (Clinical presentation of Asthma)

Chronic Asthma

initial classification of this asthma severity is based on current disease impairment and future risk.

Acute asthma

asthma that can present rapidly (within 3–6 hours), but deterioration more commonly occurs over a longer period, even days or weeks

pulsus paradoxus, diaphoresis, and cyanosis

In acute asthma patients may present with (3)

Spirometry

is required for diagnosing asthma in patients older than 5 years because the medical history and physical examination are not reliable for characterizing the status of lung impairment or excluding other diagnose

FVC (forced vital capacity) less than 70 % (0.70) and a decrease in FEV (forced expiratory volume) less than 80%

Asthma diagnosis FEV/FVC airway limitation percentages

inhalation

Direct airway administration of asthma medications through__________ is the most efficient route and minimizes systemic adverse effects.

metered dose (MDI), dry powder (DPI), soft mist (SMI), nebulizer

Inhaled asthma medications are available in (4)

Metered dose inhaler

most commonly prescribed device for asthma, requires hand-breath coordination and is usually multi dose. 5 yrs old and above

Dry powder inhaler

breath actuated requires adequate inspiratory flow (varies by device)

soft Mist inhaler

aerosol or fine mist, without a propellant, less hand-breath coordination than metered-dose inhalers. 6 years old and above

small volume nebulizer

passively deliver inhaled medication to the lungs in a fine mist, does not require hand-breath coordination or any specific technique. Less portable, needs a power source, longer treatment times and requires daily cleaning

relievers

inhaled short acting beta agonists (relievers or controllers?)

relievers

short acting anticholinergics (relievers or controllers?)

relievers

methylxanthines (relievers or controllers?)

controllers

inhaled corticosteroids (relievers or controllers?)

controllers

inhaled long-acting b- agonists (relievers or controllers?)

controllers

leukotrienes modifiers (relievers or controllers?)

controllers

sustained release theophylline (relievers or controllers?)

controllers

systemic glucocorticosteroids (relievers or controllers?)

Controllers

Anti-IgE (relievers or controllers?)

low dose ICS-formoterol or low dose ICS taken whenever SABA is taken

treatment for asthma symptoms less than twice a month

daily low dose inhaled corticosteroid (ICS) or as needed low-dose ICS-formoterol. Daily leukotriene receptor antagonist (LTRA) or low dose ICS taken whenever SABA taken as alternative.

treatment of asthma if symptoms twice a month or more, but less than daily

low-dose LABA or medium dose ICS or low dose + LTRA

treatment for asthma for symptoms most days or waking with asthma once a week or more

medium dose ICS-LABA, High dose ICS, add-on tiotropium or add-on LTRA

treatment for asthma id symptoms most days or waking with asthma once a week or more or low lung function.

short course OCS (oral corticosteroids)

__________ may also be needed for patient presenting with severely uncontrolled asthma

high dose ICS-LABA refer for phenotypic assessment add on therapy, e.g. tiotropium, anti-IgE, anti-IL5/5R, anti-IL4R

treatment for severe asthma symptoms

laboured breathing

Asthma means “___________” in Greek

inflammatory disorder

asthma as ‘a chronic ____________ of the airways which occurs in susceptible individuals

Chronic asthma

Symptoms include episodes of dyspnea, chest tightness, coughing (particularly at night), wheezing, or a whistling sound when breathing. These often occur with exercise but may occur spontaneously or in association with known allergens

Acute severe asthma

Uncontrolled asthma can progress to an acute state in which inflammation, airway edema, mucus accumulation, and severe bronchospasm result in profound airway narrowing that is poorly responsive to bronchodilator therapy

extrinsic asthma

when an allergen is thought to be the cause of their asthma. This is more common in children with a history of atopy, where triggers, such as dust mite, cause IgE production. Other environmental factors are also important, such as exposure to rhinovirus during the first 3 years of life.

‘Intrinsic asthma’

develops in adulthood, with symptoms triggered by non-allergenic factors such as a viral infection, irritants which cause epithelial damage and mucosal inflammation, emotional upset which mediates excess parasympathetic input or exercise which causes water and heat loss from the airways, triggering mediator release from mast cells.

Mast cell

components are released as a result of an IgE antibody-mediated reaction on the surface of the cell. Histamine and other mediators of inflammation are released from this, for example, leukotrienes, prostaglandins, bradykinin, adenosine and prostaglandin-generating factor of anaphylaxis, as well as various chemotactic agents that attract eosinophils and neutrophils

macrophage

release prostaglandins, thromboxane and platelet-activating factor (PAF

platelet activating factor (PAF)

appears to sustain bronchial hyperreactivity and cause respiratory capillaries to leak plasma, which increases mucosal oedema. also facilitates the accumulation of eosinophils within the airways, a characteristic pathological feature of asthma.

Eosinophils

release various inflammatory mediators such as leukotriene C4 (LTC4) and PAF. Epithelial damage results and thick viscous mucus is produced that causes further deterioration in lung function.

cell derived mediators

play a role in causing marked hypertrophy and hyperplasia of bronchial smooth muscle (these structural changes are described as ‘airway remodelling’)

peak flow meter

is a useful means of self-assessment for the patient. It gives slightly less reproducible results than the spirometer but has the advantage that the patient can do regular tests at home with a hand-held meter. measure PEF

Short-acting β2-agonists

are the most effective bronchodilators. Aerosol administration enhances broncho selectivity and provides more rapid response and greater protection against provocations (eg, exercise, allergen challenges) than systemic administration.

Albuterol and other inhaled short-acting selective β2- agonists

are indicated for intermittent episodes of bronchospasm and are the treatment of choice for acute severe asthma and EIB. Regular treatment (four times daily) does not improve symptom control over as-needed use

Formeterol and salmeterol

are inhaled longacting β2-agonists for adjunctive longterm control for patients with symptoms who are already on low to medium doses of inhaled corticosteroids prior to advancing to medium- or high-dose inhaled corticosteroids.

Inhaled corticosteroids

are the preferred long-term control therapy for persistent asthma because of potency and consistent effectiveness;

Systemic corticosteroids

are indicated in all patients with acute severe asthma not responding completely to initial inhaled β2-agonist administration (every 20 min for 3 or 4 doses

prednisone

a systemic corticosteroid 1 to 2 mg/kg/day (up to 40–60 mg/ day), is administered orally in two divided doses for 3 to 10 days

Theophylline (methylxanthines)

appears to produce bronchodilation through nonselective phosphodiesterase inhibition.

Ipratropium bromide and tiotropium bromide (anticholinergics)

produce bronchodilation only in cholinergic-mediated bronchoconstriction. Anticholinergics are effective bronchodilators but are not as effective as β2-agonists. They attenuate but do not block allergen or exercise-induced asthma in a dose-dependent fashion.

Cromolyn sodium

has beneficial effects that are believed to result from stabilization of mast cell membranes. It inhibits the response to allergen challenge as well as EIB but does not cause bronchodilation

Cromolyn sodium (mast cell stabilizer)

has beneficial effects that are believed to result from stabilization of mast cell membranes. It inhibits the response to allergen challenge as well as EIB but does not cause bronchodilation

Zafirlukast (Accolate) and montelukast (Singulair) (leukotriene modifiers)

are oral leukotriene receptor antagonists that reduce the proinflammatory (increased microvascular permeability and airway edema) and bronchoconstriction effects of leukotriene D4

Zileuton (Zyflo)

is a 5-lipoxygenase inhibitor; use is limited due to potential for elevated hepatic enzymes, especially in first 3 months of therapy, and inhibition of metabolism of some drugs metabolized by CYP3A4.

Omalizumab (Xolair)

is an anti-IgE antibody approved for treatment of allergic asthma not well controlled by oral or inhaled corticosteroids

Diskus- 4 yrs old

Elipta- 12 yrs old

Flexhaler- 6 yrs old

Respidick- 4 yrs old

Twisthaler- 4 yrs old

Spiriva handhaler- adult

Turbohaler- adult

Diskus-

Elipta-

Flexhaler-

Respidick-

Twisthaler-

Spiriva handhaler-

Turbohaler-

COPD

is a disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases

chronic obstructive airways disease (COAD), chronic obstructive lung disease (COLD)

COPD is a general term that covers a variety of other disease labels including ____________ and ____________

0.7/ 70%

Airway obstruction with a reduced FEV1/FVC ratio of less than ____

80%

f FEV1 is more than or equal _____ of predicted normal, a diagnosis of COPD should only be made in the presence of respiratory symptoms, for example breathlessness or cough

chronic bronchitis and emphysema

two principal condition of COPD

Chronic bronchitis

chronic or recurrent excess mucus secretion with cough that occurs on most days for at least 3 months of the year for at least 2 consecutive years

Emphysema

abnormal, permanent enlargement of the airspaces distal to the terminal bronchioles, accompanied by destruction of their walls, without fibrosis.

imbalance of anti-protease, inflammation response, oxidative stress

inhaled noxious particles can cause (3)

smoking

the major risk factor of COPD that causes oxidative stress

oxidative stress

increase in activated neutrophil and macrophage, imbalance or reduction in anti protease activity leading to constriction of airway

protease and anti protease

is both part of the normal function, in which its imbalance leads to increase of destructive _________ and decrease in _________.

AAT (alpha-1 anti-trypsin)

is an antiprotease that inhibits trypsin and elastase. deficiency can lead to unopposed proteases that results into the destruction of alveolar walls and lung parenchymal cells. Leading to emphysema

Inflammation

present in the lungs of the smoker but not all, In COPD it is amplified by genes

neutrophils

COPD primary mediators are _________

Tobacco smoking

is the most important and dominant risk factor in the development of COPD but other noxious contribute.

(no of cigarettes smoked per day/ 20) x no of years in smoking

How to compute total pack years

chronic cough and sputum production

the two initial symptoms of COPD

milder

physical exam may be normal in patients with _________ stages in COPD.

barrel chest

if severe cases of COPD patients may have cyanosis of mucosal membranes, development of a “___________” due to hyperinflation of the lungs.

increased sputum volume

dyspnea

increased sputum purulence

chess tightness

Malaise

COPD exacerbation (5)

lung function test, spirometry

_________is used to test in assisting with diagnosis of COPD , _________is used to confirm the diagnosis

Vital capacity (VC)

the volume of air inhaled and exhaled during maximal ventilation;

Forced vital capacity (FVC)

the volume of air inhaled and exhaled during a forced maximal expiration after full inspiration;

Residual volume (RV)

the volume of air left in the lungs after a maximal exhalation.

more than 15 hours a day for stable COPD patients with resting hypoxemia

long term oxygen therapy duration

blood eosinophil count

biomarker for efficacy of inhaled corticosteroid

Chronic bronchitis

clinical presentation of COPD that have daily productive cough 3 months to 2 consecutive years, cyanosis, hypoxemia or hypoconxima, “blue bloater”

emphysema

clinical presentation of COPD that has prominent dyspnea, overly oxygenated, “pink puffer”

short acting bronchodilator (SABA)

Group A pharmacotherapy for the management of COPD

long acting bronchodilator (LABA or LAMA)

Group B pharmacotherapy for the management of COPD

ICS (inhaled corticosteroids) or LAMA

Group B pharmacotherapy for the management of COPD

LAMA or LABA +LAMA or ICS+LABA

Group D pharmacotherapy for the management of COPD

Short acting bronchodilators

initial therapy for COPD

long acting bronchodilators

therapy if short acting bronchodilators are not effective

Albuterol (Salbutamol)

levalbuterol

terbutaline (cutaneous)

bitolterol

pirbuterol

sympathomimetics (B2 receptors) short acting (5)

salmeterol, formoterol and arformoterol

sympathomimetics (B2 receptors) long acting (3)

Indacaterol

ultra long acting agent that requires only once-daily dosing.

Ipratropium bromide

is the primary short-acting anticholinergic agent used for COPD. It has a slower onset of action than short-acting β2-agonists (15–20 min vs 5 min for albuterol). has a more prolonged effect than short-acting β2-agonists. Recommended dose via MDI is two puffs four times daily with upward titration often to 24 puffs/day. Solution for nebulizer

Tiotropium bromide

is a long-acting agent that protects against cholinergic bronchoconstriction for more than 24 hours.

Aclidinium bromide

is a long-acting agent administered twice daily using the Press Air DPI multi-dose device

Corticosteroid

reduce capillary permeability to decrease mucus, inhibit release of proteolytic enzymes from leukocytes, and inhibit prostaglandins. appropriate for short term systemic use for acute exacerbation, and inhalational therapy for chronic stable COPD.

Corticosteroid

should be avoided to be used in COPD management because of risks

inhaled corticosteroid therapy

may be beneficial in patients with severe COPD at high risk of exacerbation (Groups C and D) who are not controlled with inhaled bronchodilators.