Respiratory diseases affect the airways, lung parenchyma, pulmonary vasculature, and respiratory mechanics. They represent a leading cause of morbidity and mortality globally, with chronic respiratory diseases affecting over 500 million people. This article provides comprehensive coverage of major respiratory conditions, their pathophysiology, clinical presentations, diagnostic approaches, and treatments.

3D illustration of SARS-CoV-2 virus — Illustration of SARS-CoV-2 coronavirus morphology. Respiratory infections caused by viruses, bacteria, and fungi are among the most common reasons for healthcare visits worldwide. Source: CDC.

Asthma

Parameter	Detail
Definition	Chronic inflammatory airway disease characterized by variable airflow obstruction, bronchial hyperresponsiveness, and respiratory symptoms
Prevalence	300 million worldwide; 10% of children, 5% of adults
Pathophysiology	Inflammation (eosinophils, mast cells, Th2 lymphocytes, IgE), airway remodeling (subepithelial fibrosis, smooth muscle hypertrophy, mucus gland hyperplasia), airway hyperresponsiveness

Asthma Severity Classification (Pre-Treatment)

Severity	Symptom Frequency	Nighttime Awakenings	SABA Use	Activity Limitation	Lung Function
Intermittent	<2 days/week	<2x/month	<2 days/week	None	FEV1 >80%, FEV1/FVC normal
Mild persistent	>2 days/week but not daily	3-4x/month	>2 days/week but not daily	Minor	FEV1 >80%
Moderate persistent	Daily	>1x/week (not nightly)	Daily	Some	FEV1 60-80%
Severe persistent	Throughout the day	7x/week	Several times/day	Extremely limited	FEV1 <60%

Asthma Control Classification

Parameter	Well Controlled	Partly Controlled	Uncontrolled
Daytime symptoms	<2 days/week	>2 days/week	Throughout the day
Nighttime awakenings	<2x/month	1-3x/week	>4x/week
SABA rescue use	<2 days/week	>2 days/week	Several times/day
Activity limitation	None	Some	Extremely limited
FEV1 or peak flow	>80% predicted	60-80%	<60%
Exacerbations/year	0-1	2-3	>3

Stepwise Asthma Management (GINA)

Step	Preferred Controller	Alternative	Reliever
1	As-needed low-dose ICS-formoterol	Low-dose ICS whenever SABA taken	As-needed low-dose ICS-formoterol
2	Regular low-dose ICS + as-needed SABA	LTRA, or low-dose ICS taken whenever SABA taken	As-needed SABA
3	Low-dose ICS-LABA	Medium-dose ICS, or low-dose ICS + LTRA	As-needed SABA
4	Medium-dose ICS-LABA	High-dose ICS, add tiotropium, or add LTRA	As-needed SABA
5	High-dose ICS-LABA + LAMA; consider add-on therapies	Add anti-IgE (omalizumab), anti-IL5 (mepolizumab, benralizumab), anti-IL4R (dupilumab), anti-TSLP (tezepelumab)	As-needed SABA

Asthma Medications

Drug Class	Mechanism	Examples	Role
SABA (short-acting beta-agonists)	Beta-2 agonist, bronchodilation	Albuterol, levalbuterol	Acute symptom relief
LABA (long-acting beta-agonists)	Beta-2 agonist, 12-24h bronchodilation	Salmeterol, formoterol, vilanterol, indacaterol	Controller (must use with ICS)
ICS (inhaled corticosteroids)	Anti-inflammatory	Fluticasone, budesonide, beclomethasone, mometasone, ciclesonide	Controller (first-line)
ICS-LABA combination	Both	Fluticasone/salmeterol, budesonide/formoterol, fluticasone/vilanterol, mometasone/indacaterol	Controller
LAMA (long-acting muscarinic antagonists)	Anticholinergic	Tiotropium, umeclidinium, glycopyrrolate	Add-on controller
LTRA (leukotriene receptor antagonists)	Block leukotriene receptors	Montelukast, zafirlukast	Controller (alternative)
Biologics	See below	—	Severe asthma
Oral corticosteroids	Systemic anti-inflammatory	Prednisone	Severe exacerbations (short courses)

Biologics for Severe Asthma

Biologic	Target	Dosing	Phenotype	Eosinophil Requirement
Omalizumab	IgE	SC every 2-4 weeks	Allergic asthma	No
Mepolizumab	IL-5	SC every 4 weeks	Eosinophilic	>=150 cells/mcL
Benralizumab	IL-5R	SC every 4 weeks x3, then every 8 weeks	Eosinophilic	>=300 cells/mcL
Dupilumab	IL-4R alpha	SC every 2 weeks	Type 2 inflammation	>=150 cells/mcL or FeNO >=25
Tezepelumab	TSLP	SC every 4 weeks	All severe asthma (no phenotype restriction)	Not required

Chronic Obstructive Pulmonary Disease (COPD)

Anterior view of the lungs from Gray's Anatomy — Anterior view of the lungs showing the trachea, bronchi, and pulmonary lobes. Understanding lung anatomy is essential for diagnosing and managing obstructive lung diseases such as COPD and asthma. Source: Gray's Anatomy (1918).

Parameter	Detail
Definition	Heterogeneous lung condition characterized by persistent respiratory symptoms and airflow limitation due to airway and/or alveolar abnormalities
Global prevalence	400 million; 3rd leading cause of death worldwide
Primary cause	Cigarette smoking (80-90% in developed countries)
Other risk factors	Biomass fuel exposure, occupational exposures, alpha-1 antitrypsin deficiency, air pollution, frequent childhood respiratory infections

Emphysema vs Chronic Bronchitis

Feature	Emphysema	Chronic Bronchitis
Pathologic definition	Destruction of alveolar walls, enlarged airspaces, loss of elastic recoil	Hypertrophy/hyperplasia of mucus glands, inflammation of bronchial walls, increased mucus production
Clinical definition	—	Cough with sputum production for >=3 months in 2 consecutive years
Dominant symptom	Dyspnea on exertion (progressive)	Chronic cough, sputum production
Body habitus	Thin (pink puffer)	Plethoric (blue bloater)
Chest exam	Hyperinflation, hyperresonance, distant breath sounds	Rhonchi, wheezes, prolonged expiration
Gas exchange	Normal PaO2 early, PaCO2 normal/low (puffing)	Hypoxemia common, hypercapnia common
Cor pulmonale	Late (causes death earlier)	Early and common
Hematocrit	Normal/high	High (polycythemia from chronic hypoxemia)
CXR	Hyperinflation, flattened diaphragms, increased retrosternal air space	Increased bronchovascular markings, normal diaphragm position

COPD Assessment (GOLD)

Spirometric Grade	FEV1 (% Predicted)
GOLD 1 (Mild)	>=80%
GOLD 2 (Moderate)	50-79%
GOLD 3 (Severe)	30-49%
GOLD 4 (Very Severe)	<30%

GOLD Group Classification (ABCD)

Group	Exacerbation History	mMRC	CAT	Initial Pharmacotherapy
A	0-1 (no hospitalization)	0-1	<10	Bronchodilator (SABA, SAMA, LABA, or LAMA)
B	0-1 (no hospitalization)	>=2	>=10	LABA + LAMA
E	>=2 or >=1 with hospitalization	Any	Any	LABA + LAMA (+/- ICS if eosinophils >=300)

COPD Pharmacotherapy

Drug Class	Examples	Effect on Dyspnea	Effect on Exacerbations	Effect on FEV1	Effect on Mortality
SABA	Albuterol	Yes	No	Short-term increase	No
SAMA	Ipratropium	Yes	No	Short-term increase	No
LABA	Salmeterol, formoterol, indacaterol, olodaterol	Yes	No	Yes	No
LAMA	Tiotropium, umeclidinium, glycopyrrolate	Yes	Yes	Yes	No
LABA/LAMA	Combinations	Yes	Yes	Yes	No
ICS (inhaled corticosteroid)	Fluticasone, budesonide	No	Yes (if eosinophil >=300)	Minimal	No (may increase pneumonia)
LABA/ICS	Combinations	Yes	Yes	Yes	No
LABA/LAMA/ICS	Triple therapy (single inhaler)	Yes	Yes	Yes	Yes (for triple vs ICS/LABA in ETHOS, IMPACT)
PDE4 inhibitor	Roflumilast	No	Yes (chronic bronchitis, frequent exacerbations)	Minimal	No
Macrolide	Azithromycin	No	Yes (non-smokers)	No	No
Mucolytics	N-acetylcysteine, carbocisteine	No	Possibly (frequent exacerbations)	No	No

Non-Pharmacologic COPD Management

Intervention	Effect
Smoking cessation	Most important intervention; slows FEV1 decline
Pulmonary rehabilitation	Improves dyspnea, exercise capacity, quality of life; reduces hospitalization
Long-term oxygen therapy (LTOT)	Improves survival (if PaO2 <55 mmHg or <60 with cor pulmonale); use >=15 hours/day
Non-invasive ventilation (NIV)	For chronic hypercapnic respiratory failure; improves survival and hospitalization
Lung volume reduction surgery (LVRS)	For upper-lobe predominant emphysema with low exercise capacity
Endobronchial valves	Minimally invasive lung volume reduction for selected patients
Lung transplantation	End-stage COPD (BODE index 7-10)

Pulmonary Embolism (PE)

Parameter	Detail
Definition	Occlusion of pulmonary arteries by thrombus (usually from deep veins of lower extremities)
Risk factors	VTE triads: stasis, hypercoagulability, endothelial injury; surgery, cancer, immobility, pregnancy, OCP, inherited thrombophilia, previous VTE
Clinical presentation	Dyspnea (sudden), pleuritic chest pain, cough, hemoptysis, syncope; signs: tachypnea, tachycardia, hypoxia, DVT signs

PE Severity and Management

Severity	Hemodynamics	RV Strain	Biomarkers	Management
Low risk (PESI class I-II)	Stable	No	Negative (troponin, BNP)	Anticoagulation alone; consider early discharge
Intermediate-low risk	Stable	Yes (echo or CT)	Negative	Anticoagulation, monitor for decompensation
Intermediate-high risk	Stable	Yes	Positive	Anticoagulation, consider thrombolysis if deterioration
High risk (massive)	Hypotension/shock	Yes	Positive	Thrombolysis (alteplase) or embolectomy

Wells Criteria for PE

Clinical Sign	Points
Clinical signs of DVT	3
PE as likely or more likely than alternative diagnosis	3
Heart rate >100	1.5
Immobilization/surgery within 4 weeks	1.5
Previous DVT/PE	1.5
Hemoptysis	1
Cancer (active, treatment within 6 mo, palliative)	1

Interpretation: Traditional: >6 = high (PE likely); <=6 = low (unlikely); Two-tier: >4 = PE likely; <=4 = PE unlikely.

Sleep Apnea

Parameter	Obstructive Sleep Apnea (OSA)	Central Sleep Apnea (CSA)
Mechanism	Upper airway collapse despite respiratory effort	Absent or reduced respiratory effort (no central drive)
Common causes	Obesity (most common), craniofacial abnormalities, tonsillar hypertrophy, neuromuscular disease	Heart failure (Cheyne-Stokes), opioid use, stroke, high altitude
Apnea definition	>10 sec pause in airflow with continued respiratory effort	>10 sec pause with no respiratory effort
Symptoms	Loud snoring, witnessed apneas, gasping/choking, excessive daytime sleepiness, morning headache, nocturia	Similar but often less snoring; insomnia, fatigue

OSA Severity (AHI)

Severity	AHI (events/hour)	Minimum SpO2	Management
Mild	5-15	>=85%	Lifestyle (weight loss, position therapy, avoid alcohol); consider oral appliance
Moderate	15-30	80-84%	PAP therapy (CPAP, APAP, BiPAP); oral appliance alternative
Severe	>30	<80%	PAP therapy; consider surgery if PAP fails

Interstitial Lung Disease (ILD)

Category	Examples	Key Features
Idiopathic pulmonary fibrosis (IPF)	Usual interstitial pneumonia (UIP) pattern	Progressive; honeycombing on HRCT; poor prognosis; antifibrotics (pirfenidone, nintedanib)
Connective tissue disease-ILD	RA, scleroderma, Sjogren, SLE, myositis	Treat underlying CTD; immunosuppression; mycophenolate, cyclophosphamide, rituximab
Hypersensitivity pneumonitis	Bird fancier’s lung, farmer’s lung	Antigen avoidance; corticosteroids; immunosuppression if chronic
Sarcoidosis	Non-caseating granulomas	Variable course; corticosteroids; methotrexate, biologics
Pneumoconioses	Asbestosis, silicosis, coal worker’s pneumoconiosis	Prevention; exposure avoidance; supportive care
Drug-induced ILD	Amiodarone, methotrexate, bleomycin, nitrofurantoin, immune checkpoint inhibitors	Drug discontinuation; corticosteroids
Cryptogenic organizing pneumonia (COP)	Organizing pneumonia	Dramatic response to corticosteroids; good prognosis

IPF Diagnostic Criteria

Criterion	Finding
HRCT pattern	UIP: basal-predominant, subpleural, honeycombing, traction bronchiectasis, reticulation
Histopathology (if needed)	UIP: patchy fibrosis, fibroblastic foci, honeycombing
Exclusion of other causes	No environmental exposure, CTD, drug cause
Progression	Worsening dyspnea, FVC decline, DLCO decline, or acute exacerbation

Cystic Fibrosis (CF)

Parameter	Detail
Definition	Autosomal recessive disorder caused by mutations in CFTR gene (chloride channel)
Incidence	1:3,000-4,000 (Caucasian); 1:20-30 carrier frequency
Pathophysiology	Defective CFTR -> reduced chloride secretion, increased sodium absorption -> thick, dehydrated secretions -> airway obstruction, infection, inflammation -> bronchiectasis

CFTR Mutation Classes

Class	Defect	Examples	CFTR Modulator Response
I	No protein production	G542X, W1282X	No
II	Defective processing (ER retention)	F508del (most common, 70% of alleles)	Partial (Trikafta)
III	Defective regulation (channel gating)	G551D	Yes (Kalydeco)
IV	Defective conduction	R117H, R334W	Partial
V	Reduced protein synthesis	A455E	Partial
VI	Reduced stability	4326delTC	Unknown

CF Clinical Features

System	Manifestations
Respiratory	Recurrent infections (S. aureus, H. influenzae, P. aeruginosa, B. cepacia), bronchiectasis, hemoptysis, pneumothorax, respiratory failure (leading cause of death)
GI/Pancreatic	Pancreatic insufficiency (85%), meconium ileus (10-15%), DIOS, CF-related diabetes (20-30% by age 30), cirrhosis
Reproductive	Congenital bilateral absence of vas deferens (CBAVD) in males; reduced fertility in females
Other	CF-related diabetes, osteoporosis, clubbing, chronic sinusitis, nasal polyps

CFTR Modulator Therapies

Drug	Target	Efficacy
Ivacaftor (Kalydeco)	Potentiator (class III, gating mutants)	Significant improvement in lung function, sweat chloride, weight; 50% reduction in exacerbations
Lumacaftor/ivacaftor (Orkambi)	Corrector + potentiator (F508del)	Modest improvement (2-4% FEV1); high side effect burden
Tezacaftor/ivacaftor (Symdeko)	Corrector + potentiator (F508del)	Similar to Orkambi but better tolerated
Elexacaftor/tezacaftor/ivacaftor (Trikafta)	Dual corrector + potentiator (F508del + up to 177 other mutations)	10-15% FEV1 improvement; 60% exacerbation reduction; transformative for 90% of CF population

Acute Respiratory Distress Syndrome (ARDS)

Parameter	Detail
Definition	Acute onset of hypoxemic respiratory failure with bilateral pulmonary infiltrates not fully explained by cardiogenic pulmonary edema
Etiology	Direct (pneumonia, aspiration, inhalation injury, pulmonary contusion) vs Indirect (sepsis, pancreatitis, major trauma, transfusion, burns, drug overdose)
Berlin Definition	Acute onset (within 1 week), bilateral opacities on CXR/CT, PEEP >=5, PCWP <=18 mmHg or no clinical evidence of left atrial HTN

ARDS Severity (Berlin Criteria)

Severity	PaO2/FiO2 (with PEEP >=5)	Mortality
Mild	200-300 mmHg	25-30%
Moderate	100-200 mmHg	35-40%
Severe	<100 mmHg	45-55%

ARDS Management

Intervention	Evidence/Effect
Low tidal volume ventilation (6 mL/kg IBW)	Decreases mortality by 20% (ARMA trial)
Plateau pressure <=30 cmH2O	Limits barotrauma
PEEP optimization	Prevents atelectrauma; higher PEEP for moderate-severe
Prone positioning (for severe ARDS)	Decreases mortality by 50% if applied early (PROSEVA)
Neuromuscular blockade (cisatracurium)	Improves oxygenation; mortality benefit (ROSE trial: negative for routine use but beneficial in early severe ARDS)
Fluid conservative strategy (ARDSNet FACTT)	More ventilator-free days, no mortality benefit
Corticosteroids (dexamethasone)	Decreases mortality, ventilator days (DEXA-ARDS)
ECMO	Rescue therapy for refractory severe ARDS (EOLIA trial)
Inhaled vasodilators (NO, prostacyclin)	Rescue therapy; improves oxygenation but no mortality benefit