Pulmonary System and Asthma Quiz

Respiratory System

• Respiration is controlled by spontaneous rhythmic discharges from the respiratory center in the medulla.
• This is modulated by input from higher central nervous system (CNS) centers and vagal afferents from the lungs.
• Input considers the partial pressure of carbon dioxide in arterial blood (PACO2) and oxygen (PAO2).
• Voluntary control can be superimposed on automatic breathing regulation.
• This implies connections between the cortex and motor neurons that innervate the muscles of respiration.
• Irritant receptors and C fibers respond to chemical irritants and cold air, and to inflammatory mediators.

Autonomic Innervation of Airways

• Parasympathetic innervation predominates in the bronchial smooth muscle.
• Pharmacologically, M3 receptors are the most important.
• These receptors are located on bronchial smooth muscles and glands.
• They mediate bronchoconstriction and mucus secretion.
• A distinct population of NANC nerves also regulates the airways.
• Bronchodilators released by these nerves include vasoactive intestinal polypeptide and nitric oxide.

Sympathetic Innervation of Airways

• β2-adrenoceptors are abundantly expressed on human airway smooth muscle, mast cells, epithelium, glands, and alveoli.
• β agonists relax bronchial smooth muscle, inhibit mediator release from mast cells, and increase mucociliary clearance.

Sensory Fibres in Lungs

• Non-myelinated sensory fibers linked to irritant receptors in the lungs release tachykinins such as substance P, neurokinin A, and B.
• These act on smooth muscle, secretory, and inflammatory cells to produce inflammation.

Pulmonary Diseases

• Common symptoms include shortness of breath, wheezing, chest pain, cough, and sometimes sputum production or hemoptysis (blood in sputum).
• Treatment focuses on the underlying disease, but symptomatic treatments like cough relief may be necessary.

Asthma

Definition

• Asthma is characterized by recurrent, reversible airway obstruction in response to irritant stimuli too weak to affect non-asthmatics.
• Patients experience intermittent attacks of wheezing, shortness of breath (especially when exhaling), and sometimes coughing.
• Acute attacks are reversible, but the underlying condition can progress to a chronic state in some.

Cellular Elements in Asthma

• Many cells and cellular elements play a role in asthma, particularly many mast cells, eosinophils, neutrophils, T lymphocytes, macrophages, and epithelial cells.

Asthma Symptoms

• Symptoms include coughing (especially at night or early morning), wheezing, breathlessness, chest tightness.
• There's a wide range of severity, from occasional mild bouts to daily wheezing despite medication.

Etiology of Asthma

• Childhood-onset (atopic): Includes positive family history of asthma and allergies (e.g., tree and grass pollen, house dust mites, pets, molds) and IgE-mediated response to environmental allergens.
• Adult-onset: Usually lacks a positive family history; sometimes occurs due to workplace exposures to irritants (e.g., wood dust, chemicals).

Other Asthma Types

• Environmental asthma, exercise-induced asthma, occupational asthma, aspirin-induced asthma

Pathogenesis of Asthma

• The classic immunologic model describes asthma as a disease mediated by IgE.
• After exposure to an asthma precipitating factor (like an allergen), IgE is produced and binds to mast cells in the airway mucosa.

Asthma Airway Changes

• Injury to the airways (with an accumulation of inflammatory cells, edema, and swelling) leads to bronchospasm.

Asthma Inflammatory Mediators

• Inflammatory mediators are released from bronchial mast cells, T lymphocytes, and epithelial cells.
• These mediators direct the migration and activation of other inflammatory cells, particularly eosinophils, to the airways.
• Eosinophils release biochemicals like major basic protein (ECP) and eosinophil cationic protein (ECP). These cause airway injury, including epithelial damage, mucus hypersecretion, and increased smooth muscle reactivity.

Early and Late Asthmatic Response

• Early-phase: bronchoconstriction develops immediately after allergen exposure and improves after an hour.
• Late-phase (3-6 hours later): more sustained bronchoconstriction, associated with inflammatory cell influx into the bronchial mucosa, and increased bronchial reactivity lasting weeks.

Pulmonary Function Tests

• Spirometry is used to evaluate lung, thorax, and respiratory muscle function, particularly during forced exhalation, to measure how much air a person can exhale during a forced breath..
• The FEV1 (forced expiratory volume in one second) and FEV1/FVC (ratio of FEV1 to forced vital capacity) are key measures.
• Healthy individuals typically exhale 75-80% of their vital capacity within 1 second.
• Peak expiratory flow (PEF) measures the maximal flow rate during forced exhalation.

Treatment Goals

• Reduce impairment (symptoms and effects)
• Reduce risk of future problems.

Asthma Treatment: Drugs

• Sympathomimetic agents: Relax airway smooth muscle, help inhibit the release of bronchoconstricting mediators, and inhibit microvascular leakage (e.g., epinephrine, ephedrine, isoproterenol, salbutamol, terbutaline, metaproterenol, salmeterol, formoterol).
• Methylxanthines: Inhibit phosphodiesterase (PDE) enzymes, thereby increasing cAMP and cGMP levels, leading to smooth muscle relaxation. Actions of methylxanthines include inhibition of inflammatory activity and stimulation of cardiac function (e.g., theophylline).
• Antimuscarinic agents: Block the effects of acetylcholine by acting on muscarinic receptors, preventing bronchoconstriction; also help to reduce mucus secretion. Examples include atropine and ipratropium bromide.
• Corticosteroids: Broad anti-inflammatory effects, mediated partly by inhibiting the production of inflammatory cytokines. Reduce bronchial reactivity. Examples include budesonide, ciclesonide, beclomethasone, flunisolide, fluticasone, mometasone, and triamcinolone.
• Cromolyn and nedocromil: Inhibit mast cell activation.
• Leukotriene pathway inhibitors (e.g., zileuton, zafirlukast, montelukast): Reduce the effects of leukotrienes to help with bronchoconstriction, increased bronchial reactivity, mucosal edema, and mucus hypersecretion.
• Anti-IgE monoclonal antibodies (e.g., omalizumab): Decrease IgE binding to mast cells, lowering asthma exacerbations and reducing steroid needs.

Methods of Administration and Dosage Forms

• Drugs can be inhaled or oral as inhalers, oral tablets, or injections.
• Dosage forms and delivery methods have different side-effect profiles.

Acute Asthma Management

• Hospitalized patients need continuous monitoring and treatment.
• Oxygen, inhalers, IV hydrocortisone/methylprednisolone are common treatments.
• General anesthesia and mechanical ventilation may be necessary in severe cases.

Other Issues (Asthma)

• Asthma can be intermittent or persistent.
• Severity of asthma can vary considerably.
• Asthma treatment must be tailored to the patient's needs.

Mechanism of Action (Drugs)

• Individual mechanisms of action vary for each drug class.
• Common mechanisms include smooth muscle relaxation, inhibiting inflammatory mediators, controlling inflammation, or other pathways specific to the type of medication.

Side Effects (Drugs)

• Different side effects are possible with different types of drugs.

Diagnosis and Monitoring

• History: Symptoms (wheezing, chest tightness, shortness of breath, coughing, mucus production), Pattern (perennial, seasonal), Onset (how it begins), Duration and Frequency, Diurnal Variations (nocturnal/early morning), and precipitating factors.
• Pulmonary function tests (PFTs):
  • Spirometry measures lung function, particularly forced exhalation measures (FEV1, FVC, FEV1/FVC ratio), and peak expiratory flow (PEF).
• Other tests: Blood tests for allergens.

Other considerations

• Inhaled corticosteroids are controllers but are only effective when administered..
• Oral corticosteroids and some other therapies are for use in acute or long-term cases, as directed by clinicians.