PULM/HEME EXAM 2 🫁

What regulates bronchodilation in airway smooth muscle?

The sympathetic (adrenergic) nervous system.

Which receptors mediate bronchodilation, and what activates them?

β2-adrenergic receptors; activated by epinephrine.

What regulates bronchoconstriction in airway smooth muscle?

The parasympathetic (cholinergic) nervous system.

Which receptors mediate bronchoconstriction, and what stimulates them?

Muscarinic M3 receptors; stimulated by acetylcholine.

What other fibers regulate bronchial smooth muscle tone besides adrenergic and cholinergic systems?

Nonadrenergic, noncholinergic (NANC) fibers in the respiratory tree.

Which mediators act as bronchoconstrictors from NANC fibers?

Neurokinin A, calcitonin gene-related peptide, substance P, bradykinin, tachykinin, neuropeptide Y.

Which mediators act as bronchodilators from NANC fibers?

Nitric oxide (NO)

Vasoactive intestinal polypeptide (VIP)

Which interleukin induces eosinophil proliferation and survival?

IL-4.

Which interleukin recruits eosinophils?

IL-5.

Which interleukin activates eosinophils?

IL-33.

Which interleukin stimulates TH2 & ILC2 function?

IL-25.

Which interleukin chemoattracts TH2 cells?

IL-33.

Which cytokine activates DCs to promote TH2 differentiation?

TSLP.

Which interleukin induces B cells to produce IgE?

IL-4.

👉 Why? IgE is what arms mast cells against allergens — when allergens show up, mast cells dump histamine and leukotrienes, causing bronchoconstriction. At the same time, IL-4 keeps eosinophils alive to prolong the attack.

Which interleukin induces goblet cell hyperplasia, mucus production, and smooth muscle hyperplasia?

IL-13.

👉 Why? IL-13 makes airways clogged with mucus and thickened with extra smooth muscle. This means air can't flow normally → wheezing, coughing, and harder-to-treat asthma.

Which interleukins initiate macrophage switch to M2?

IL-4 & IL-13.

What is the role of airway epithelial cells in immunity?

First line of innate immune sensing; produce cytokines (IFN-α, β, γ, IL-33, IL-25, TSLP, CCL2, CCL20).

What do Toll-like receptors (TLR) recognize?

Nucleic acids (TLR3, TLR7, TLR9) and lipopolysaccharide (TLR4).

What do RIG-like receptors (RLR) recognize?

Replicating RNA viruses.

What do protease-activated receptors (PAR) detect?

Nonfungal allergens; elicit allergic airway inflammation in response to proteolytic allergens.

Allergens (like P for Pollen)

What do NOD-like receptors (NLR) detect?

Bacterial peptidoglycans.

Bacteria

What do C-type lectin receptors detect?

Fungal patterns.

Fungus

Where are dendritic cells located in the airway and what do they do?

On the basolateral side of the epithelium; sample antigens with pseudopodia and express pattern recognition receptors.

What are cDCs (conventional dendritic cells)?

Finish development in the lung; can induce TH2 & TH17 helper cells OR TH1, TH2, T cytotoxic, and Treg cells depending on subtype.

Conventional found in the lung

What are pDCs (plasmacytoid dendritic cells)?

Fully develop in bone marrow; maintain tolerance to harmless antigens and drive antiviral responses.

What are moDCs (monocyte-derived dendritic cells)?

Present in steady-state lungs; important in antiviral responses and can contribute to pulmonary immunopathology.

be MINDFUL of these

Both alveolar and interstitial macrophages are ________

fetal yolk-sac derived and express pattern recognition receptors.

What are the key functions of alveolar macrophages (AM)?

Sit at the frontlines of alveoli → must clean up inhaled debris (phagocytosis), present antigens to T cells, and balance between defense (inflammation) vs. tolerance (activate Tregs).

Their M1/M2 switch lets them go pro-inflammatory or repair mode depending on signals.

Interstitial macrophages

Deeper in parenchyma → act as "regulators" of lung environment.

Interstitial macrophages have a high _______ baseline that makes them immunosuppresive, preventing overreaction.

IL-10/IL-6/IL-1ra

Interstitial macrophages also respond to _______

hypoxia, important for lung tissue repair and vascular balance.

M1/M2 and IM1/IM2 diversity

Reflects macrophages' ability to polarize → either drive inflammation (M1/IM1) or promote tissue repair/tolerance (M2/IM2).

What are the 3 subsets of innate lymphoid cells (ILCs) in the airway?

ILC1, ILC2, and ILC3.

What do ILC1 cells do?

Include NK cells; release IFN-γ and TNF-α; increase in lung pathology.

What do ILC2 cells do?

Produce IL-4, IL-5, IL-9, IL-13; activated by IL-25 and IL-33; increase with allergic lung inflammation.

What do ILC3 cells do?

Produce IL-22 and/or IL-17 in response to IL-23; help develop secondary lymphoid tissue; may contribute to COPD.

What do Tc (cytotoxic T cells) do?

CD8+ effector cells; kill virally infected or transformed (tumor) cells.

What do Th (helper T cells) do?

CD4+ cells that direct immune responses.

What do Th1 cells do?

Produce IFN-γ, IL-2, TNF-α; promote cellular responses with Tc and Th cells.

What do Th2 cells do?

Guide antibody production (allergy/parasite).

Produce IL-4, IL-5, IL-6, IL-9, IL-13

What do Th17 cells do?

Promote neutrophil migration, chemokine secretion, enhance Th2 responses.

Produce IL-17

What is the Hygiene Hypothesis (Missing Old Friends Hypothesis) of Allergy?

Lack of infection or exposure to microbes humans co-evolved with favors allergic disease.

What infections are key in this hypothesis for restoring immune balance?

Mycobacteria and helminths → stimulate TH1 responses and regulatory mechanisms.

How do multiple/repetitive infections during development affect allergy/asthma risk?

Shape the immune system and reduce risk of allergic disease.

What role do nonpathogenic organisms play?

Help regulate the immune system (e.g., Prevotella copri).

_____ asthma is IgE mediated and also called “allergic asthma.”

Extrinsic (Type 2)

In intrinsic (non-allergic) asthma, serum IgE levels are ______.

normal or low

Intrinsic asthma is also called ______ asthma.

Type 1/17

Intrinsic asthma often has later onset and shows ______ predominance.

female

The precipitating factor for intrinsic asthma is often ______.

unknown (may be environmental, stress, or hormones)

Occupational asthma requires ______ to a specific chemical (e.g., isocyanates, flour, latex, glue).

sensitization

______-induced occupational asthma develops after a single, very high exposure to an irritant chemical and is not immune related.

Irritant

In intrinsic (non-allergic) asthma, serum IgE levels are ______.

normal or low

Intrinsic asthma is also called ______ asthma.

Type 1/17

Intrinsic asthma often has later onset and shows ______ predominance.

female

What causes airway narrowing in asthma?

Bronchospasm, mucosal edema, mucus plugging

What causes hyperinflation in asthma?

Functional residual capacity rises; helps keep airways open

What happens to the accessory muscles during asthma?

Accessory muscles used to maintain hyperinflation

What happens to gas exchange during asthma?

Hypoxemia due to V/Q mismatch during severe attacks

Late Phase Asthma Response

Inflammatory cascade causing persistent obstruction

Modifiable Factors that can lead to Severe Asthma

Uncontrolled asthma symptoms

High SABA use (≥3 canisters/year)

Poor adherence to ICS

Incorrect inhaler technique

Smoking

Allergen exposure

Air pollution

Physiological Factors that can lead to Severe Asthma

Low FEV1 (<60% predicted)

High bronchodilator response

Elevated eosinophils

High FeNO

Comorbidities which can contribute to asthma severity

Obesity, rhinosinusitis, GERD, food allergy, pregnancy

Medical History which can lead to Severe Asthma

Prior ICU/intubation

≥1 severe exacerbation in last 12 months

Medication risks that can lead to severe Asthma

Frequent oral corticosteroids

Long-term high-dose ICS (esp. with CYP450 inhibitors)

Developmental Risks which can lead to worse Asthma

Preterm birth, low birth weight, chronic mucus hypersecretion

Symptoms characteristic of asthma

• Multiple: wheeze, shortness of breath, cough, chest tightness

• Worse at night/early morning

• Variable over time/intensity

• Triggers: viral infections, exercise, allergens, weather changes, cold air, laughter, irritants (smoke, exhaust, strong smells)

SABA (albuterol, levalbuterol) MOA

β2 agonist → bronchodilation

SABA (albuterol, levalbuterol) ADR

Tremor, tachycardia, hypokalemia

Fastest onset, preferred reliever

SABA

Anticholinergic (ipratropium) MOA

Blocks M3 receptors → ↓ bronchoconstriction

Anticholinergic (ipratropium) ADRs

Dry mouth, blurred vision

ICS ADR 

Thrush, dysphonia, systemic effects (high dose)

ICS MOA

↓ airway inflammation

LABA ADR

Tremor, tachycardia

LABA MOA

Long β2 agonism

LABA (formoterol, salmeterol, vilanterol) are always combined with what?

ICS

Systemic steroids (prednisone, methylprednisolone) MOA

Broad anti-inflammatory

Systemic steroids (prednisone, methylprednisolone) ADRs

Hyperglycemia, mood changes, Cushing’s (chronic use)

Leukotriene modifiers (montelukast, zafirlukast, zileuton) MOA

Block leukotriene signaling

Leukotriene ADRs

Neuropsychiatric (montelukast), hepatotoxicity (zafirlukast, zileuton)

Theophylline MOA

PDE inhibition, ↑ cAMP

Theophylline ADRs

Nausea, arrhythmias, seizures

Note for Theophylline

Narrow therapeutic index

Biologics for Asthma MOA

Target IgE, IL-5, IL-4R, TSLP

Biologics for Asthma ADR

Hypersensitivity, eosinophilia

LAMA (tiotropium) MOA

Block M3 receptor

LAMA (tiotropium) Common ADRs

Dry mouth, headache

Airsupra®

Budesonide/Albuterol → ICS + SABA

Symbicort®

Budesonide/Formoterol → ICS + LABA

Advair

Fluticasone/Salmeterol → ICS + LABA

Dulera®

Mometasone/Formoterol → ICS + LABA

Breo Ellipta®

Fluticasone/Vilanterol → ICS + LABA

Trelegy Ellipta®

Fluticasone/Vilanterol/Umeclidinium → ICS + LABA + LAMA

Breztri Aerosphere

Beclomethasone/Formoterol/Glycopyrrolate → ICS + LABA + LAMA

Chronic (Stepwise, GINA 2024) Asthma Treatment

Step 1-2: AIR only (budesonide-formoterol or budesonide-albuterol) PRN

Step 3: Daily low-dose ICS-formoterol + PRN

Step 4/5: Higher-dose ICS-formoterol, add-ons (LAMA, biologics)

Acute Exacerbation Asthma Treatment

• Early ↑ reliever (SABA/ICS-formoterol)

• Add oral steroids 5–7 days if moderate-severe

• Remove trigger, monitor PEF

• Discharge: ICS optimization, follow-up in 2–7 days

Exercise-Induced Bronchospasm (EIB)

• Regular ICS helps prevent

• Pretreat with SABA or low-dose ICS-formoterol before exercise

What are the brand names of albuterol?

ProAir®, Ventolin®, Proventil®

What is the brand name of levalbuterol?

Xopenex®