Asthma


History


Definitions


Prevalence


Risk Factors for Asthma

Hygiene Hypothesis

Infections

Atopy

Diet

Obesity

Genetics

Environmental Exposures


Asthma Triggers

Allergens

Food/Food-Related Allergens

Inhalant Allergens

Occupational Allergens (see Asthma-Occupational, [[Asthma-Occupational]])

Emotional Factors

Hormonal Fluctuations

Irritants

Medications

Respiratory Infections

Temperature/Weather

Other


Agents that Provoke Airway Narrowing

Etiologic Classification

1) Persistent Asthma: continuing symptoms + chronic airway abnormality (abnormal dose response to histamine/methacholine or increased variation of daily PEFR)
-Generally incurable (some cases remit during adolescence)
2) Obstructed Asthma: symptoms + airflow limitation that persist after maximal treatment with bronchodilators and PO steroids/pathologic changes unknown
3) Episodic Asthma: periodic episodes of symptoms (usually requiring treatment) + no detectable abnormality of airway function between episodes
-Common type during the pollen season/ sometimes seen early in occupational asthma/ described in non-allergic patients/ pathologic changes are unknown
4) Asthma in Remission: past history of asthma without symptoms or therapy for >12 months (usually have some residual airway hyper reactivity)
5) Potential asthma: typically moderate airway hyperreactivity without symptoms or history of asthma
-Particularly occurs in atopic patients
6) Trivial Wheeze: mild or transient wheezing that do not require treatment + normal airway function (absence of airway hyper reactivity)
7) Extrinsic (Atopic) Asthma: asthma in atopic patient (may have attacks in response to non-allergen provoking agents)/ usually positive family history of atopy or asthma/evidence if IgE-mediated mechanisms
8) Occupational Asthma: episodic or persistent asthma due to workplace sensitizer (symptoms and airway narrowing are demonstrated by specific provocation with substance)
9) Intrinsic Asthma: asthma in non-atopic patient (often adult onset)/ usually negative family history of atopy or asthma/ usually no evidence of IgE-mediated mechanisms
-May follow severe respiratory illness/ may be refractory


Physiology

Airway Remodeling

Physiologic Manifestations

Airflow Limitation


Pathology


Diagnosis

Arterial Blood Gas (ABG) (see Arterial Blood Gas, [[Arterial Blood Gas]])

Bronchoscopy (see Bronchoscopy, [[Bronchoscopy]])

Chest X-Ray (see Chest X-Ray, [[Chest X-Ray]])

Chest CT (see Chest Computed Tomography, [[Chest Computed Tomography]])

Complete Blood Count (CBC) (see Complete Blood Count, [[Complete Blood Count]])

Electrocardiogram (EKG) (see Electrocardiogram, [[Electrocardiogram]])

Fraction of Exhaled Nitric Oxide (FeNO)

Serum Immunoglobulin E (IgE) (see Serum Immunoglobulin E, [[Serum Immunoglobulin E]])

Peak Expiratory Flow Rate (PEFR) (see Peak Expiratory Flow Rate, [[Peak Expiratory Flow Rate]])

Pulmonary Function Tests (PFT’s) (see Pulmonary Function Tests, [[Pulmonary Function Tests]])

Skin Testing

Sputum Gram Stain/Culture


Clinical Manifestations

Otolayngologic Manifestations

Paradoxical Vocal Fold Motion (Vocal Cord Dysfunction) (see Paradoxical Vocal Fold Motion, [[Paradoxical Vocal Fold Motion]]): if present

Pulmonary Manifestations

Allergic Bronchopulmonary Aspergillosis (ABPA)

Cough (see Cough, [[Cough]])

Dyspnea (see Dyspnea, [[Dyspnea]])

Other Manifestations

Classification:
– Mild: 4.0 PD20FEV1/inhaled steroid need <0.5 mg per day
– Moderate: symptoms most days/25% variation in PEFR/ <1.0 PD20FEV1/inhaled steroid need 2.0 mg per day
– Very Severe: recent hospitalization/nocturnal BD need/>35% variation in PEFR/ <0.1 PD20FEV1/inhaled steroid need 2.0 mg per day

Persistent Asthma (insidious onset or episodic/symptoms lasting for months-years):

-Symptoms/Signs: H+P does not usually fully elucidate the severity of disease/usually responsive to ß-agonists (typically regular use)
1) Wheezing:
2) Dyspnea: dyspnea correlates poorly with FEV1 (patients who are poor perceivers of airflow obsruction are at increased risk of bad outcomes)
3) Chest Tightness:
4) Prolonged Expiratiory Phase:
5) Cough: this is the only presenting symptom in 57% of cases and is often the prominent symptom
-Cough may be the first sign of worsening control (particularly occurring at night)
6) Pulsus Paradoxus (due to high negative intrathoracic pressure):

Nocturnal Asthma

-This is associated with asthma severity (and is an indicator of overall control)
-Usually early AM (circadian variation in airway muscle tone, inflammation, catecholamine and cortisol secretion, supine posture, snoring, GERD, or waning medication levels)
-In dogs, REM autonomic hyperactivity with fluctuation in airway smooth muscle tone occurs but REM is not clearly associated with nocturnal asthma in humans

Episodic (Seasonal) Asthma (episodic exacerbations lasting days-weeks, symptom-free intervals without therapy):

-Seasons: Spring (grass or tree pollen)/ Fall (ragweed pollen)
-Allergic rhinitis may also be present

Occupational Asthma: See Occupational Asthma

-Known asthmatics that develop symptoms at work (due to dust, etc.) are classified as having Work-Aggravated Asthma (not Occupational Asthma)

Cough-Variant Asthma

-Common type in children and elderly

Exercise-Induced Asthma (aka Exercise-Induced Bronchoconstriction): this is typically viewed as an indicator of the adequacy of asthma control

-Exercise-induced bronchoconstriction occurs in 70-80% of patients with actively symptomatic asthma (it is more likely to occur in patients with moderately-severely increased airway responsiveness)
-Nasal breathing decreases exercise-induced bronchoconstriction
-Repeated exercise usually decreases exercise-induced bronchoconstriction (exercise refractoriness usually lasts around 4 hrs)

Aspirin-Sensitive Asthma: ASA produces airway narrowing in 2-10% of adult (most have severe chronic asthma) and childhood asthmatics

-Associated with (nasal symptoms are less prominent in children): hyperplastic rhinitis/nasal polyps/sinusitis
-Epidemiology: having both nasal polyps + asthma = 40% risk of having ASA-sensitivity
–Most patients have history of perennial rhinitis dating back to 20 s, often after a viral illness
-Pathogenesis: due to decreased PG production
-Clinical: some asthmatics patients actually improve with ASA (unclear why)
–Samter’s Syndrome (most patients are adults): asthma + vasomotor rhinitis/nasal polyposis + ASA sensitivity
–Diagnosis is usually made by history + ASA challenge: ASA ingestion results in asthma exacerbation, rhinitis, facial flushing, periorbital edema, and conjunctival injection
-Treatment:
1) ASA Avoidance: best treatment
-NSAIDs with minimal COX-inhibition may be safely used: sodium salicylate, salicylamide, choline magnesium trisalicylate
-Although lower doses of acetaminophen are safe in these patients, higher doses (>1000 mg) may manifest cross-reactivity with ASA
-Selective COX-2 inhibitors have not been studied in this setting
2) ASA Desensitization: improves both asthma and nasal polyps
-Ideal after polypectomy, as it delays recurrence of polyps up to 6 yrs
3) Cromones: somewhat protective
4) Leukotriene antagonists: protective
5) Diet Screening: ASA sensitivity may predispose sensitivity to tartrazine/benzoates (diet may need to be screened for salicylates, etc.)

Asthma in Pregnancy: asthma during pregnancy increases preterm births, low birth weight (low FEV1 during pregnancy increases risk of IUGR), and neonatal mortality

-Pathophysiology of Pregnancy:
1) ABG: pCO2 is usually <35 with slight metabolic acidosis (pH ranges from 7.4-7.45) and normal pO2
a) Increased VE (begins during first trimester, up to 48% increase by term) with Normal-Mildly Elevated RR: due to progesterone
b) Increased VT (30-35% above normal, to around 450-600 ml) with Increased A-P Diameter of Chest
2) Swan:
a) PVR decreased (up to 35% by late pregnancy):
b) Increased CO and blood volume with normal PCWP and CVP
3) PFT s/Exercise Testing:
a) FRC and RV are decreased (with preserved FEV1 and VC)
b) Increased oxygen consumption (rises to 40-100% above normal) + Increased CO2 Production (rises to 30-50% above normal by third trimester)
4) Symptoms:
a) Dyspnea is common in all pregnancies (due to progesterone secreted by placenta)
b) Pregnancy may improve asthma (due to progesterone-induced bronchodilation and increased circulating histaminase)
-Treatment:
–Asthma Drugs: safe in pregnancy (steroids increase cleft palate in animals/ only effect in humans is a decrease birth weight by 300-400 g)
–Uterine Contractions: common during exacerbation
–Preterm Labor: treat with Magnesium Sulfate (it avoids excessive use of ß2-agonists and it produces bronchodilation)

Reversible Airway Restriction

-Rare presentation with low lung volumes, normal or near normal expiratory airflow, increased lung elastance, and decreased lung compliance that may reverse with bronchodilators or steroids
-The mechanism of reversible restriction in humans is not known, it likely involves closure of terminal lung units due to alveolar duct constriction (ie, pneumoconstriction ) similar to what has been observed in cats
[Kaminsky DA, Irvin CG. Anatomic correlates of reversible restrictive lung disease. Chest. 1993;103:928-931
Hudgel DW, Cooper D, Souhrada J. Reversible restrictive lung disease simulating asthma. Ann Intern Med. 1976;85:328-332]

Acute Asthma Exacerbation

-Symptoms/Signs: wheezing (may be absent in severe disease)/dyspnea/cough (may be only symptom)/pulsus paradoxus (>15 suggests severe attack)
-Difficult to distinguish from acute bronchiolitis in children without asthma history
-Previous life-threatening episode portends poorer prognosis
-Patient is usually better judge of attack severity than physician
-Patients who are poor perceivers of airflow obsruction are at increased risk of bad outcomes (including death)

Complications of Asthma


Treatment

Address Underlying Factors Contributing to Asthma Pathogenesis

Management of Specific Asthma Situations

Management of Exercise-Induced Asthma

Management of Asthma in Pregnancy

Management of Asthma in the Peri-Operative Period

Management of Asthma Risks with Scuba Diving

Asthma Biomarkers, Associated Phenotypes, and Predictors of Response to Asthma Therapies

Allergen Immunotherapy (see Allergen Immunotherapy, [[Allergen Immunotherapy]])

Antihistamines (see H1-Histamine Receptor Antagonists, [[H1-Histamine Receptor Antagonists]])

Asthma Action Plans

Cromones (Cromoglycates)

Short-Acting β2-Adrenergic Receptor Agonists (SABA) (see β2-Adrenergic Receptor Agonists, [[β2-Adrenergic Receptor Agonists]])

Long-Acting β2-Adrenergic Receptor Agonists (LABA) (see β2-Adrenergic Receptor Agonists, [[β2-Adrenergic Receptor Agonists]])

Short-Acting Anti-Muscarinic/Anti-Cholinergic (SAMA) Agents (see Muscarinic Antagonists, [[Muscarinic Antagonists]])

Long-Acting Anti-Muscarinic/Anti-Cholinergic (LAMA) Agents (see Muscarinic Antagonists, [[Muscarinic Antagonists]])

Leukotriene Modifier Agents

Theophylline (Theo-Dur) (see Theophylline, [[Theophylline]])

Inhaled Corticosteroids (see Corticosteroids, [[Corticosteroids]])

Systemic Corticosteroids (see Corticosteroids, [[Corticosteroids]])

Omalizumab (Xolair) (see Omalizumab, [[Omalizumab]])

General Information

Anti-Interleukin-4 (IL-4) Therapy

Dupilumab (see Dupilumab, [[Dupilumab]])

Anti-Interleukin-5 (IL-5) Therapy

Mepolizumab (Nucala) (see Mepolizumab, [[Mepolizumab]])

Reslizumab (Cinqair) (see Reslizumab, [[Reslizumab]])

Anti-Interleukin-13 (IL-13) Therapy

Lebrikizumab (TNX-650) (see Lebrikizumab, [[Lebrikizumab]])

Bronchial Thermoplasty (see Bronchial Thermoplasty, [[Bronchial Thermoplasty]])

Hypotherapy

Acupuncture

Step-Down Therapy

Agents With Unclear Clinical Benefit in Asthma

Specific Treatment of Asthma Exacerbation

Magnesium Sulfate (see Magnesium Sulfate, [[Magnesium Sulfate]])

Oxygen (see Oxygen, [[Oxygen]])

Short-Acting β2-Adrenergic Receptor Agonists (SABA) (see β2-Adrenergic Receptor Agonists, [[β2-Adrenergic Receptor Agonists]])

Short-Acting Anti-Muscarinic/Anti-Cholinergic Agents (SAMA) (see Muscarinic Antagonists, [[Muscarinic Antagonists]])

Systemic Corticosteroids (see Corticosteroids, [[Corticosteroids]])


Pregnancy

Mortality Rates: lower mortality rate in USA compared to other countries (possibly due to different patterns of aerosol bronchodilator use)

Risk of Fatal Asthma: greatest in those asthmatics with highest degree of airway hyperresponsiveness and FEV1 lability (rather than in those with severe, fixed airway obstruction)


References

General

Treatment

General

Allergen Immunotherapy

Long-Acting Muscaninic Antagonists (LAMA)

Theophylline

Inhaled Corticosteroids (see Corticosteroids, [[Corticosteroids]])

Omalizumab (see Omalizumab, [[Omalizumab]])

Dupilumab (see Dupilumab, [[Dupilumab]])

Mepolizumab (see Mepolizumab, [[Mepolizumab]])

Reslizumab

Lebrikizumab (see Lebrikizumab, [[Lebrikizumab]])

Bronchial Thermoplasty

Magnesium (see Magnesium Sulfate, [[Magnesium Sulfate]])

Macrolides

Other Treatment