3. Pulmonology

“The act of breathing is living”

3.1 Acute Respiratory Failure

Acute onset of shortness of breath (SOB) or acute respiratory decompensation is a common emergency condition. This can occur due to multiple etiologies, as following:

  • Exacerbation of asthma or chronic obstructive pulmonary disease (COPD).

  • Respiratory infection (viral/bacterial).

  • Lung injury.

  • Foreign body aspiration.

  • Heart failure and pulmonary edema.

  • Respiratory depressants such as opiate poisoning or barbiturates.

  • Tiring diaphgramatic muscles which can occur in all causes of severe persistent hypoxemia, e.g., in later stages of asthma exacerbation or pulmonary embolism.

  • Acute neuro-muscular weakness with involvement of diaphgram, that can occur in conditions like myasthenic crisis or Guil-lain–Barre syndrome.

Lung auscultation is a very powerful diagnostic tool

Lung auscultation findings

In what area?


Decreased breath sounds

In all lung zones In specific zones

  • Hypoventilation

  • Complete obstruction of central airway

  • Severe COPD or asthma

In specific zones

  • Atelectasis

  • Pleural effusion (additional finding is dullness to percussion)

  • Pneumothorax (additional finding is tympanic sound on percussion)

  • Misplaced endotracheal tube

Increased breath sounds (inspiration and expiration equally heard = bronchial breath sounds)

In specific zones

Consolidation of lung segments due to lobar pneumonia Additional findings include:

  • Increased vocal and tactile fremitusa

  • Dullness to percussion

Wheezes or rhonchi

In all lung zones In specific zones

Bronchospasm, which can be caused by

  • Asthma

  • COPD

  • Parasympathomimetics (e.g., organophosphate poisoning)

  • β blocker overdose

  • Bronchiolitis in children

  • Generalized bronchiectasis Localized bronchiectasis

Crackles or rales

Bilateral basilar crackles

  • Fluid accumulation in alveoli due to congestive heart failure

  • Interstitial lung disease with bibasilar predominance (Velcro-crackles)

In specific zones Generalized

  • Pneumonia

  • Atelectasis

  • Localized bronchiectasis


  • Interstitial lung disease (Velcro crackles)

  • Generalized bronchiectasis

Stridor = noisy breathing (often so loud that it can be heard without a stethoscope)

Due to incomplete upper or middle-respiratory tract obstruction

  • Foreign body

  • Infection (e.g., epiglottitis, croup)

  • Laryngomalacia

  • Subglottic stenosis

aThese exam findings are due to increased conduction of vibration by consolidated lung. In the consolidated part of the lung

  • with auscultation, patient’s spoken words and whispered sounds are heard louder (termed as bronchophony and whispering pectoriloquy, respectively)

  • with percussion, more vibration is felt (increased tactile fremitus).

Management steps for acute respiratory failure

  • Pulse oximetry (which measures oxy-hemoglobin saturation), chest X-ray (CXR), and on occasions arterial blood gas (ABG), are important initial diagnostic tools to evaluate the severity and the cause of respiratory compromise.

  • Step up of supplemental oxygen therapy: This is used to maintain oxygen saturation (SaO2) to > 88 to 92% or PaO2 > 60 mmHg.

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How much supplemental oxygen is needed to maintain adequate oxygenation tells us how sick the patient is; for example, the respiratory status of a patient requiring 100% oxygen delivered through a nonrebreather mask is much worse than a patient on 4 L of oxygen by nasal cannula.

3.1.1 Bilevel Positive Airway Pressure aka Noninvasive Positive Pressure Ventilation

Bilevel positive airway pressure (BiPAP) is a noninvasive method of ventilation that can deliver up to 100% oxygen with application of positive airway pressure through a tight-fitting mask. The mask is very easy to put on and take off (since it is a mask), in contrast to invasive intubation. In acute pulmonary edema, BiPAP has the added benefit of decreasing preload. BiPAP increases intrathoracic pressure and decreases venous return to right heart.

1 Note that BiPAP cannot be used in following cases:

Obtunded patient who cannot control their airway.

• Patients with excessive secretions.

• Agitated or uncooperative patient.

• Hemodynamic instability.

In these cases, NSIM is endotracheal intubation.

3.1.2 Mechanical Ventilation


  • Severe hypoxemia, hypercarbia, or respiratory acidosis unresponsive to general noninvasive measures.

  • Patients who have hemodynamic instability (such as hypotension).

  • Patients who have altered mental status and cannot protect their airways.

An endotracheal tube is inserted in the patient’s airway and connected to a ventilation machine.

In most ventilator settings, the following parameters are looked at

Tidal volume (TV)

It is the volume of air delivered through ventilation machine in each breath. Recommended tidal volume is 6–8 cc/kg of predicted body weight.

2 Note: in ARDS the recommend TV is not more than 6 cc/kg of predicted body weight.

Too high TV can cause:

  • Barotrauma

  • Can increase intrathoracic pressure resulting in decreased venous return to heart, thereby. decreasing cardiac output

  • Hyperventilation (respiratory alkalosis)

Too low TV can cause atelectasis, and hypoventilation (respiratory acidosis)

Respiratory rate (RR)

It is generally set at 8–14/min

Too high RR can result in:

  • Incremental air trapping in each successive breath causing auto-PEEPa

  • Hyperventilation (respiratory alkalosis)

Too low RR can cause hypoventilation (respiratory acidosis)

FiO2 (fraction of inspired oxygen)

Generally preferred at < 60% to decrease risk of oxygen toxicity

Positive end expiratory pressure (PEEP)

Minimal PEEP of 5 cm H2O is used in all patients on mechanical ventilation to prevent end expiratory alveolar collapse. As PEEP is increased, it helps to recruit collapsed alveoli to improve gas exchange and oxygenation. Higher levels of PEEP (15–20 cm H2O) may be required to improve oxygenation, with the goal to reduce higher FiO2 to prevent oxygen toxicity.
However, note that higher PEEP can be associated with the following complications:

  • Increased risk of rupture of alveoli with subsequent development of tension pneumothorax (pulmonary barotrauma)

  • Hypotension: high intrathoracic pressure impedes venous return into the right heart, which leads to subsequent decrease in preload of the left heart and cardiac output

a Auto-PEEP can occur when the respiratory rate is set too high and/or if there is increased airway resistance (due to COPD, asthma,

3 To prevent auto-PEEP in COPD/asthma, it is recommended to use lower TV and RR, even at the expense of mild hypoventilation and respiratory acidosis, as long as pH is > 7.2. This strategy is known as permissive hypercapnia.

or narrow endotracheal tube).

In this case, the lungs do not have enough time to expire the inhaled air, and hence, more and more air gets trapped in each consecutive respiratory cycle, incrementally increasing the intrathoracic pressure. This can result in barotrauma and hypotension, similar in pathophysiology to high PEEP.

In a nutshell

  • Tidal volume (TV) and respiratory rate (RR) are used to control ventilation (getting rid of CO2).

  • FiO2 and positive end expiratory pressure (PEEP) are used to control oxygenation.

  • Minute ventilation = RR × TV.

Clinical Case Scenarios

  1. An intubated patient is found to be hypoxic and hypotensive. Exam reveals severe wheezing. It appears that ventilator settings needs to be adjusted. What is the likely cause of hypoxia and hypotension in this patient?

  2. An intubated patient is found to be hypoxic and hypotensive. Exam reveals no breath sounds on one side of the lung. What is the likely cause of hypoxia and hypotension in this setting?

    Intubated patient has hypoxia and absent breath sounds in one side of the lung.

  3. What are the differential dx?

  4. How would you differentiate in between them?

3.1.3 Modes of Ventilation

Assisted-control mode of ventilation (ACMV): This mode is commonly used for starting patient on mechanical ventilation and when patient is ready for weaning

4 Do not choose synchronized-intermittent mandatory ventilation as a weaning mode for ventilation as this method is not used anymore.

(prior to initiation of low-pressure support ventilation). The clinician determines preset TV and RR. Patients may initiate breathing, but preset TV is delivered. Patient can also breathe over the vent. For example, ACMV mode is set at TV of 500 cc and RR of 12.

  • If patient’s own breathing rate is 10, then patient will get additional 2 breaths delivered with TV of 500 cc each. In this case minute ventilation = 0.5 L × 12/min = 6 L/min.

  • If patient’s own breathing rate is 15, then the extra 3 breaths that patient initiates, he/she will get 500 cc of preset TV in each breath (minute ventilation = 0.5 × 15). In this case, patient is said to be breathing over the vent.

Pressure control ventilation (PCV): The ventilator delivers preset pressure support in each breath. Tidal volume is not specified.

Stepwise management of ventilation

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a Try to keep the ratio of 60% FiO2 to 10 of PEEP, and 40% FiO2 to 5 of PEEP. Most of the time exam CCS will involve a question with 60 FiO2 with 10 of PEEP scenario.

b Reducing FiO2 is the first step to reduce risk of oxygen toxicity. But note that if PEEP was mistakenly set at 20 and FiO2 is set at 60%, and if oxygenation is adequate then NSIM is to decrease PEEP in this case; but this is an extreme example only.

c Recommended tidal volume is 6 to 8 cc/kg of predicted body weight. FYI an average adult’s normal tidal volume is 500 mL.

d Remember permissive hypercapnia in ARDS, COPD, and asthma.

Clinical Case Scenarios

5. Patient is intubated for ARDS. His vent settings are PEEP of 10, FiO2 of 80% and RR of 12. ABG reveals PaO2 of 90. What is the NSIM?

6. A 65-year-old female with asthma exacerbation is currently intubated. RR of 20. ACMV mode is set at RR of 13 per minute and TV of 500 cc. ABG shows pH of 7.26, PaCO2 of 60 mmHg, PaO2 70 mm Hg. What is the NSIM?

Ventilator Weaning

Consider weaning when the patient

  • Can maintain oxygenation with FiO2 < 40 to 50%, PEEP of ≤ 5 cm H2O.

  • Does not have excessive secretions.

  • Is awake enough to control airway.

  • Is hemodynamically stable (no or minimal vasopressor support).

To determine whether patient is ready for extubation, a spontaneous breathing trial is used with ventilation mode changed to low-pressure support ventilation. It is very similar to BiPAP, with positive pressure given during inspiration and expiration and TV/RR is completely dependent on the patient’s own respiratory effort.

During the first few hours of low-pressure support ventilation, rapid shallow breathing index (RSBI) ratio is calculated.RSBI = RR/TV (in liters). It is a ratio that is used to assess readiness of a patient to get extubated.

RSBI > 105

Patient is breathing rapidly (high RR) and has shallow breathing (low TV). Patients with RSBI of > 105 are likely to fail extubation

5 If ventilator weaning fails for more than 7 to 10 days, consider tracheostomy.

RSBI ≤ 105

Patient is ready for weaning. NSIM is consider extubation

Other complications of mechanical ventilation

  • Stress-induced peptic ulcers: all patients on mechanical ventilation are recommended to get prophylaxis with proton pump inhibitor or H2 receptor antagonist (e.g., famotidine).

  • Ventilator-acquired pneumonia: placing patient on semirecumbent position has been shown to decrease incidence.

  • Pneumomediastinum, pneumoperitoneum, and subcutaneous emphysema are milder forms of barotrauma and generally require supportive care only.

Clinical Case Scenarios

A 65-year-old male patient is on 5 PEEP and 40% FiO2 on ACMV mode. ABG done showed PaO2 of > 60 mmHg. Prior to morning intensive care unit (ICU) rounds the ventilator setting is changed to lowpressure support ventilation. During rounds he is found to have RR of 30 per minute and TV of 200 cc.

7. What is his RSBI?

8. What would you do next?

Next morning his RSBI is < 105 on low-pressure support. Extubation is attempted after rounds.

Intubated ARDS patient develops swelling of face and neck and eyelids. Exam reveals crepitus over the neck and face.

9. What is the NSIDx (next step in diagnosis)?

10. If CXR is negative, what is the most likely dx?

VQ mismatch

Ventilation(V) in a lung zone should be matched with perfusion (Q) in that zone. The following are the types of VQ mismatch:

Dead space


When perfusion is decreased to a well-ventilated area of the lung, then that part of the lung is defined as a dead space, where the ventilated volume of air will not participate in gas exchange. Think of this as dead air (space), which is useless. Classical example is pulmonary embolus

Anatomic or vascular shunts: blood passes from right side of heart to the left side bypassing the lungs/alveoli. This is known as right to left shunt
Examples: pulmonary AV malformation, Eisenmenger’s syndrome, cyanotic congenital heart disease, etc.
Physiological shunt: An area with no ventilation, but with continuing perfusion creates intrapulmonary physiologic shunta; blood is being passed through an area of lung with no gas exchange. This occurs when the alveoli are:

  • Collapsed (in atelectasis)

  • Filled with infiltrates (in lobar pneumonia or ARDS)

  • Filled with fluid (in pulmonary edema)

To counteract this mismatch, reactive hypoxic pulmonary vasoconstriction does occur, but remember that compensation is never complete etc.1

Dead space = high V/Q ratio as denominator (perfusion) is low

Shunt= low V/Q ratio as ventilation is low.

aHypoxemia due to anatomic/vascular shunts canot be corrected by supplemental oxygen. Physiologic shunting, on the other hand, is usually not a pure shunt. Supplemental oxygen will help in these cases.

How to find out the cause of acute respiratory failure by looking at ABG?

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aIn patients with acute respiratory distress and acute hypercapnic respiratory failure, NSIM is usually BIPAP or intubation. Patients at this stage are usually lethargic or comatose.

6 On the other hand, chronic hypercapnia +/- hypoxemia can occur in COPD, obesity hypoventilation syndrome and extrinsic lung disease (e.g., severe kyphoscoliosis). It is usually well compensated by chronic metabolic alkalosis.

bA-a gradient = Alveolar (PAO2) – arterial (PaO2) gradient. As alveolar (PAO2) is not easily obtainable, clinically the following formula is used to calculate A-a gradient = (150 – 1.25 × PaCO2) – PaO2 (the normal value is < 15 mmHg). Increased gradient (in between the oxygen content of the alveoli and the oxygen content of the systemic arteries) means that there is intrinsic lung pathology. A-a gradient is not increased in hypoventilation or high altitude.

3.1.4 Acute Respiratory Distress Syndrome

Background: Any severe local lung injury (e.g. drowning) or severe extrapulmonary pathology (e.g. severe sepsis) can cause oversecretion of inflammatory mediators into the blood stream that can activate neutrophils, which in turn release proteases and free radicals, damaging the endothelial and epithelial layers of alveoli. This leads to high protein vascular fluid leakage into the alveoli which eventually fills most of the intra-alveolar space, thereby causing significant areas of shunting. This condition is called ARDS. Histopathological picture is of diffuse alveolar damage.

7 Possible long-term sequela of ARDS is pulmonary fibrosis.


  • Systemic: severe sepsis, trauma, burns, acute pancreatitis, drug overdose, toxins, transfusion related acute lung injury (TRALI), etc.

  • Pulmonary: drowning, large volume aspiration, severe pneumonia, etc.

Diagnostic criteria

  • Acute onset: within 1 week of initial insult.

  • PaO2/FiO2 ratio of ≤ 200.

  • Bilateral infiltrates present on CXR.

  • No clinical evidence of elevated left atrial pressure, or pulmonary capillary wedge pressure (PCWP) is ≤ 18 mmHg.

Work-up: Transthoracic echocardiogram (TTE), and serum Brain natriuretic peptide (BNP) are good initial tests, as the major differential dx for ARDS is cardiogenic pulmonary edema. TTE is generally adequate to assess for evidence of heart failure. If large body habitus makes it hard to get a good quality TTE images and if assessment of volume status is needed, a Swan-Ganz catheter can help in direct measurement of cardiac pressures.

Rx: Always treat the underlying etiology. Mechanical ventilation is usually necessary. Recommended TV is 6 mL/kg of predicted body weight and plateau pressure (end inspiratory) of ≤ 30 cm H2O, even if it results in mild hypercapnia and respiratory acidosis (permissive hypercapnia is tolerated until pH is < 7.2).

8 Lower TV strategy has been shown to have better outcome.

In ARDS of newborns (aka hyaline membrane disease [HMD] of the prematurity), the primary pathology is generalized collapse of alveoli due to deficient surfactant. So CXR picture in HMD of newborn will show ground-glass appearance of the lung as opposed to ARDS of adults that will show bilateral opacities.

In patients with similar presentation, but PaO2/ FiO2 ratio is > 200 (and < 300), the dx is acute lung injury (ALI).


123 for ARDS/ALI

Clinical Case Scenarios

A 41-year-old male admitted to ICU for severe pancreatitis now develops acute onset of respiratory symptoms with increasing SOB. ABG in 100% non-rebreather mask reveals PaO2 of 40 mmHg. CXR shows diffuse bilateral infiltrates (see picture).

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Source: Heart. In: Gunderman R. Essential radiology. Clinical presentation, pathophysiology, imaging. 2nd ed. Thieme; 2000.

11. What is the NSIDx?

12. What is the likely dx?

3.2 Pulmonary Function Tests


  • • Unexplained pulmonary symptoms.

  • Monitoring known pulmonary disease.

  • Preoperative assessment prior to lung resection.

  • Differentiating between obstructive and restrictive lung disease.

    9 If a patient presents with vague respiratory complaints and has hx of smoking as well as high-risk occupation (such as working in mining industry), test of choice is spirometry. It can differentiate between obstructive (COPD) and restrictive (asbestosis associated interstitial lung) disease.

Pulmonary function test includes

  • Spirometry.

  • Flow volume loop.

  • Lung volumes.

    10 Spirometry cannot measure residual volume (RV) and any parameter that requires this value (e.g., function residual capacity or total lung capacity). This requires special techniques.

  • Diffusion-lung capacity for carbon monoxide (DLCO).

Pulmonary function test values in obstructive and restrictive lung disease



General principle

It is characterized by decrease in expiratory flow rates in PFT. Narrowing of airway disproportionately affects expiratory phase, as airway is normally narrower in expiration

One of the classic examples of restrictive lung diseases is interstitial lung fibrosis. Imagine the lung as a thick, stiff, small balloon which is very hard to inflate (to inhale) and easy to deflate (exhale), as the recoil pressure of the stiff-fibrosed lung is very high





Normal (or decreased)


FEV1/FVCa ratio


N or ↑





Functional residual capacity




Emphysema, bronchiolitis obliteransc and bronchiectasis


Primary pulmonary restrictive disorder, e.g., diffuse parenchymal lung disease (aka interstitial lung disease)


Asthmad and chronic bronchitis


Extraparenchymal lung disorderse

a FEV1/FVC = Forced expiratory volume of air in 1 sec/forced vital capacity (most important parameter we need to look at)

b DLCO is a measurement of alveolar diffusion capacity. This diffusion capacity is affected by decrease in surface area (e.g., emphysema) or decreased permeability (e.g., interstitial lung disease).

11 High DLCO occurs in polycythemia and left to right shunt.

Decreased DLCO and normal PFTs can be seen in severe anemia, or primary pulmonary vascular disorder with no parenchymal involvement (e.g., pulmonary hypertension).

c Bronchiolitis obliterans (aka obliterative bronchiolitis) is inflammatory condition of smallest airways. It can be either sudden in onset or slowly progressive. It presents with dry cough, SOB, and wheezing. Etiologies include lung, or bone-marrow transplantation, infection, connective tissue disorders, toxic fume inhalation, etc. Treatment is supportive as disease is irreversible and patients may go on to require lung transplantation.

d NSIDx after PFTs suggest obstructive airway disease is to do bronchodilator challenge (e.g., albuterol). If FEV1 increases by ≥ 12% and/or increases by 200 mL from baseline, it indicates reversible airway obstruction suggestive of asthma.



ABC of the obstructive airway disease: Asthma

Bronchiectasis, bronchiolitis obliterans

COPD (chronic bronchitis and emphysema)

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Note: These values (FEV1, FVC, etc.) obtained from PFT are used for diagnosis, prognosis, evaluating progression of disease, and treatment response. So, PFT is “the” diagnostic test of choice for most of the chronic respiratory disorders.

Abbreviations: DLCO, diffusion capacity of lung for carbon mono oxide; RV, residual volume; TLC, total lung capacity Residual volume.

Lets practice some values

  • First trick is to look only at percentage of predicted value. The normal value is usually 80 to 120% (100 +/- 20). Low is <80%. The only exception is forced expiratory volume1/forced vital capacity (FEV1/FVC) ratio, where the cut off for low value is < 70%.

  • Second trick is to first look at FEV1/FVC to categorize it as obstructive or restrictive and then look at DLCO to find out the subtype.

FEV1 (%)

FEV1/FVC (%)

DLCO (%)





FEV1/FVC is low = obstructive airway disease. DLCO low = emphysema, bronchiolitis obliterans, or extensive bronchiectasis disease




FEV1/FVC is normal = restrictive lung disease. DLCO low = diffuse parenchymal lung disease




Asthma or chronic bronchitis. NSIDx is bronchodilator challenge test




Chest wall disorder, neuromuscular issue, massive ascites or obesity hypoventilation syndrome. Note that FEV1 is low (abnormal)




Normal FEV1 with low DLCO = anemia or primary pulmonary vascular disorder


LOAD ratio (LOw FEV1/FVC ratio is obstructive airway disease.

If it helps, another way to look at this MRS is to see 70 in LO; L looks like 7. So, the cut-off value for this ratio is 70, whereas for everything else, it is 80.

3.2.1 Flow Volume Loop

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Commonly used medications for obstructive airway disease



Side effects

β2 agonists cause bronchodilation

Short-acting β2 agonist (SABA)

Albuterol, levalbuterol, metaproterenol, pirbuterol, salbutamol, albuterol, terbutaline, etc.

Tachycardia, tremors Muscle weakness due to hypokalemia
Exam scenario: patient undergoing treatment for COPD/asthma develops muscle weakness and tremors.

Long-acting β2 agonist (LABA)

Salmeterol, formoterol, vilanterol, etc.

Atropine like M-antagonists (anticholinergics) relax bronchial smooth muscles, causing bronchodilation

Short-acting muscarinic antagonist (SAMA)


Atropine like side effects:

  • Dry mouth, tremors, mydriasis

  • These causes less tachycardia than β2 agonist

  • Acute narrow-angle glaucoma

Exam scenario: patient undergoing asthma treatment in emergency department develops acute onset eye pain and redness

Long-acting muscarinic antagonist (LAMA)

Tiotropium, umeclidinium, aclidinium, etc.


ABC of the obstructive airway disease:


Bronchiectasis, bronchiolitis obliterans

COPD (chronic bronchitis and emphysema)


For β2 agonists, look for suffix +terol

Corticosteroids decrease airway inflammation

Inhaled corticosteroids

Fluticasone, beclomethasone, mometasone, budesonide, flunisolide, ciclesonide

  • Low to mid dose-inhaled steroids usually only have local side effects such as dysphonia (changes in voice) and oral candidiasis

  • High dose can cause systemic side effects similar to oral steroids

Oral corticosteroids

Prednisone, prednisolone

Frequent use (e.g., in patients with multiple exacerbation) may lead to development of drug-induced Cushing’s syndrome

Intravenous corticosteroids

Methylprednisolone or hydrocortisone


For Corticosteroids, look for suffix +sone or +ide

3.3 Asthma

Pathophysiology: A disorder of hyperactive airways due to inflammatory response to generally innocuous stimuli (such as allergens, cold, exercise, etc.), which lead to the following changes:

  • Bronchospasm

  • Airway edema

  • Mucosal hypersecretion

Depending upon the stimuli, asthma can be divided into the following categories:



Atopic (aka extrinsic or allergic) asthma

  • Attacks are precipitated by allergens (e.g., molds, dust mites, pollen, animal dander, feather, dust, food, cockroaches, etc.). MC trigger is house dust mites.

  • Patients may have history of other type I hypersensitivity reactions, such as allergic rhinitis, urticaria, or atopic dermatitis

  • Complete blood count may show eosinophilia

  • Allergy skin prick testing is recommended to find specific triggers and to avoid them. If not available, blood radioallergosorbent test, (which measures specific IgE levels to common allergens), can be done

  • Generally, this kind of asthma has better prognosis than late-onset nonatopic asthma

Intrinsic (aka idiosyncratic or nonatopic) asthma

  • Attacks are precipitated by nonimmunologic stimuli such as infections, cold air, exercise, emotional upset, etc.

Occupational asthma

  • Reaction to chemicals, irritants, or allergen exposure at work

  • Work-related symptom history should be obtained in all asthma patients

  • If this dx is suspected, NSIDx is PFTs before and after work or during vacation.

Reactive airway dysfunction syndrome

This can result from a single, accidental inhalation of large amounts of respiratory irritants like gas, smoke, fume, or vapor (chlorine gas, bleach, ammonia, etc.)

  • Dx is based upon history of exposure, and subsequent development of asthma syndrome in a patient with no prior history of pulmonary disease

Classic presentation: Acute sudden onset of wheezing and shortness of breath

12 Asthma can also present with hx of paroxysms of acute cough episodes (cough-variant asthma).

that comes and goes. In earlier stages, patients are mostly asymptomatic in between the attacks. If asthma is not properly controlled, it can progress to fixed airway obstruction and at this stage patients can have persistent SOB or wheezing.


  • PFT is most helpful in confirming the dx of asthma

  • If FEV1 or FEV1/FVC is reduced (in moderate to severe asthma), NSIM is bronchodilator challenge (e.g., albuterol). If repeat PFT shows 12% increase in FEV1 and/or increase in 200 mL from baseline, this indicates reversibility of airway obstruction, suggestive of asthma.

  • If FEV1 and FEV1/FVC is normal, then NSIDx is either

    • Bronchoprovocation test by using inhaled methacholine, mannitol or exercise testing. or

    • Serial measurement of FEV1 or peak expiratory flow (PEF) at home or in office. A variability of 20%, corresponding with symptoms is suggestive of asthma.

3.3.1 Principles of Asthma Management

  • Prevent exposure to stimuli and treat other associated comorbidities that can worsen asthma (e.g., gastroesophageal reflux disease [GERD], morbid obesity, sinusitis, etc.).

  • Prevent asthma attacks (long-term management).

  • Treat acute asthma exacerbation.

  • Diagnose and manage complications.

Long-term management of asthma

Intensity of therapy depends on frequency and timing of attacks, as shown in the table below.

Frequency of symptoms during daytime

Frequency of symptoms during nighttime

Baseline FEV1

Asthma severity


2 or less days/week

2 or less nights/month


Intermittent asthma

No daily medication; just SABA (e.g., albuterol) as needed

> 2 days/week

More than 2 nights/month


Persistent asthma (mild)

Low-dose inhaled steroids (LDIS) should be given

Daily occurrence of symptom (acute SOB and wheezing occurring at least once every day)

2 or more nights/week

Low (< 80)

Persistent asthma (moderate)

If not yet well controlled, NSIM is medium dose inhaled steroids (MDIS) + LABA

Continuous symptoms (SOB and/or wheezing throughout the day)

Frequent (nightly awakening)

< 60

Persistent asthma (severe)

High dose inhaled steroids (HDIS) + LABAb
If not yet well controlled, NSIM is oral steroidsc

aIn asthma, LABA is not used alone and is always given in combination with inhaled steroids. Using LABA alone has been shown to increase risk of asthma-related complications. In contrast, LABA can be given alone in COPD.

13 In asthma, inhaled steroids have been shown to have the maximal benefit on the patient’s long-term quality of life. They work by reducing the airway reactivity, edema, and inflammation.

bWhen patients are on HDIS evaluate for appropriateness of omalizumab (monoclonal IgG antibody to IgE). Omalizumab is indicated in patients who have evidence of allergy in skin testing and IgE levels between 30 and 700 IU/mL. If IgE levels are too low, giving antibody to IgE is useless. If IgE levels are too high, antibodies to IgE are overwhelmed by the amount of IgE .

cSome patients with severe asthma might require chronic use of systemic steroids. In these patients an FDA approved procedure, called bronchial thermoplasty can be considered, which consists of bronchoscopy-mediated application of heat to reduce smooth muscle hypertrophy and obstruction.

Abbreviations: LABA, long-acting β2 agonist; SABA, shortong-acting β2 agonist; SOB, shortness of breath.

Few notes on long-term management of asthma

  • • Use of short-acting β2 agonist (SABA) > two times/week for acute symptoms indicates poor asthma control and signals the need for step-up of therapy.

  • If asthma is well controlled, always attempt to reduct dosage or discontinue inhaled steroids. This strategy will reduce incidence of side-effects (step-down management)

  • Consider subcutaneous allergen desensitization therapy in patients with persistent atopic asthma.

  • In patients with persistent asthma, alternative therapies such as mast cell stabilizers (cromolyn or nedocromil), theophylline, and leukotriene receptor antagonist (zafirlukast and montelukast) can also be considered.

Clinical Case Scenarios

13. Patient has hx of asthma and is on low-dose inhaled steroids (LDIS). He complains of wheezing and SOB every day for the last one week. What is the severity of asthma? What is the NSIM?

14. Patient has hx of asthma and is on LDIS+ long-acting β2 agonist (LABA). Currently patient reports that for the last few months, he has had to use his rescue inhaler (albuterol) only two times per week. What is the NSIM?

15. Patient has hx of asthma and is on LDIS. Patient has FEV1 of 50 in office. She reports that this is her baseline and feels SOB throughout the day. What is the severity of asthma? What is the NSIM?

16. Patient has hx of moderate persistent asthma and is on LDIS +LABA. Patient reports waking up at least two times per week with SOB. What is the NSIM?

3.3.2 Acute Asthma Attack

Example CCS: Patient with hx of asthma comes to emergency department (ED) with acute onset of shortness of breath(sob). Exam reveals diffuse wheezing. Peak expiratory flow rate (PEFR) at beside is 220 L/minute. Patient’s predicted PEFR value is 350. Patient’s PEFR is 62% of predicted (as 220/350 = 0.62).

Algorithm for guidelines on acute asthma exacerbation management

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Legend: NSIM, next step in management; SABA, short-acting B2 agonist (albuterol); SAMA, short-acting muscarinic antagonist (e.g., ipratropium); PEFR, peak expiratory flow rate.

aIf patient improves after the first bronchodilator treatment with PEFR of > 70% of predicted or personal best, patient can be discharged without systemic steroids.

bAfter first round of SABA +/- SAMA, if patient still has persistent wheezing and no improvement, NSIM is to give steroids (oral or intravenous). Time to order CXR.

14 In asthma exacerbation, CXR is usually normal or may just show hyperinflated lungs.

cIf any of the following signs/symptoms are present, even after adequate bronchodilator therapy, NSIM is to consider intubation and IV magnesium sulfate.

• Patient has difficulty talking and cannot complete sentences due to respiratory distress.

• Altered mental status.

• Cyanosis.

• Pulsus paradoxus.

15 There is so much lung hyperinflation that it is increasing the intrathoracic pressure, leading to greater than expected drop in systolic pulse pressure (> 20 mmHg) on inspiration. (The pathophysiology is similar to auto-PEEP.)

• Inaudible or decreased breath sounds on lung exam: in this scenario, the airway obstruction is so severe that there is no air movement (clinically called silent chest).

• PaCO2 is N or ↑ : PaCO2 is low in acute asthmatic attack, due to tachypnea and hyperventilation, but if PaCO2 is N or ↑ then it is either due to severe obstruction or patient’s respiratory muscles are tiring.

16 Decision to intubate should not be made based on ABG alone. If ABG shows PaO2 of > 60 mmHg and high PaCO2, but patient is speaking in full sentences and clinically appears better, then intubation is likely not necessary. In this case, patient is likely improving from severe asthma attack and is responding to treatment.

Acute asthma management—additional points

  • Prior to discharge remember the indications for vaccination which include flu and pneumococcal vaccination (same schedule as in COPD). Also, assess underlying severity of asthma (to prescribe LDIS or MDIS or LABA, if needed).

  • Antibiotics are only indicated if there is hx suggestive of bacterial bronchitis or pneumonia.

  • Do not give mast cell stabilizers (nedocromil and cromolyn sodium) for acute episode.

3.3.3 Other Forms of Asthma

Exercise-induced asthma

SOB and wheezing occurring only during or after exercise. It happens because of mast cell degranulation and histamine-mediated airway reactivity induced by exercise

Nocturnal asthma

Rx: General asthma management principles apply here too

Pseudoallergic reaction to aspirin/NSAIDs

Pathophysiology: Aspirin/NSAIDs inhibit COX enzyme (cyclooxygenase pathway), but not the LOX (lipoxygenase) pathway. Their use may lead to overactivation of lipoxygenase pathway, with resultant overproduction of leukotrienes, which are proinflammatory to airways. This inflammation can also involve nasal passages leading to development of rhinosinusitis and inflammatory nasal polyps
Presentation scenario: new-onset episodic SOB and wheezing, and/or nasal congestion and snoring (due to rhinosinusitis/polyp). It can occur in children or adults
Diagnosis: it is made clinically; look for history of chronic aspirin/NSAIDs use (exam scenario may say some OTC pain medication)
Management: DOC is leukotriene receptor antagonist (zafirlukast and montelukast). Avoid aspirin or NSAIDs. If underlying condition requires treatment with NSAIDs or aspirin, NSIM is desensitization

Abbreviations: COX, cyclooxygenase; DOC, drug of choice; NSAID, nonsteroidal anti-inflammatory drug; OTC, over the counter; SABA, short-acting β2 agonist; SOB, shortness of breath.

Conditions presenting with asthma-like symptoms (low yield)

Patients with the following conditions can present with difficult to control asthma or worsening asthma symptoms in a previously well-controlled patient:


Eosinophilic granulomatosis with polyangiitis (formerly known as Churg–Strauss syndrome)

Chronic eosinophilic pneumonia

Allergic bronchopulmonary aspergillosis (ABPA)

Common to all

Asthma-like presentation + eosinophilia

Specific organ involvement

Lungs + other organ involvement, such as

  • Colon: colitis

  • Nerves: sensory loss

  • Upper airway: e.g., recurrent otitis media, allergic rhinitis, sinusitis, etc.

  • Skin: palpable purpura

Only lungs are involved

Only lungs are involved

Additional clues that point toward the diagnosis

Use of leukotriene antagonist therapy leads to worsening of disease

Flu like syndrome (e.g. low-grade fever, malaise), weight loss, night sweats, etc.

Increasing severity of asthma or COPD, with thick-brownish phlegm production

CXR/CT scan picture

Migratory or transient interstitial infiltrates

Infiltrates with peripheral or pleural-based distribution (it is photographic opposite of pulmonary edema which as infiltrates predominant in perihilar region)

  • Upper zone opacities

  • Findings of bronchiectasis

  • Atelectasis due to mucoid impaction


  • Serum ANCA

  • Elevated IgE

  • Biopsy of affected area confirms the dx (e.g., skin or peripheral nerve)

NSIDx is bronchoalveolar lavage which will show ≥ 25% eosinophils

  • 1st Screening test: skin prick test with aspergillus antigen, or check serum anti-aspergillus IgE antibody.

  • NSIDx: check total IgE levels (elevated), peripheral eosinophilia count, and aspergillus-specific IgG antibody

  • CT scan of chest is also done


Systemic corticosteroids

Systemic corticosteroids

  • Systemic corticosteroids

  • Itraconazole or voriconazole is indicated for patients who cannot be tapered off steroids, or who have acute ABPA exacerbation

Abbreviations: ANCA, antineutrophil cytoplasmic antibodies; COPD, chronic obstructive pulmonary disease.

3.4 Chronic Obstructive Pulmonary Disease

Pathophysiology: Long-term exposure to irritants, such as tobacco smoking, air pollution, exposure to poorly ventilated cooking and heating fires (particularly in developing world), and genetic factors can lead to an inflammatory response in the lungs, causing COPD.

17 Of all chronic smokers, 10 to 15% develop COPD. Ninety percent of COPD patients have smoking history.

It presents with chronic SOB and exercise intolerance. It typically worsens over time.

COPD comprises of emphysema and chronic bronchitis.

18 Patients with COPD may not have a clearcut mphysema or chronic bronchitis. These frequently coexist and the management is similar.


Chronic bronchitis


Destruction of alveolar walls and respiratory bronchioles with subsequent loss in diffusion surface area

Chronic airway inflammation with mucosal hypersecretion (chronic productive cough) and hypertrophy (obstruction)

Clinical features

Patients have normal oxygenation (pink) but as the lungs are hard to deflate (due to poor lung recoil and diaphragmatic flattening), patients typically must puff out the air (puffers). Hence known as “Pink puffers”

Early stage: chronic sputum production (look for this to make a clinical dx of chronic bronchitis)
Late stage: chronic hypoxemia (blue cyanotic) → reactive chronic pulmonary vasoconstriction → pulmonary HTN → right heart failure → edema (bloating)
Hence known as blue bloaters.

CXR findings

  • Decreased pulmonary vascular markings

  • Hyperinflation with diaphragmatic flattening (diaphragmatic flattening increases the work of breathing)

Increased pulmonary vascular markings

Main differentiating feature in PFTa

DLCO is decreased

DLCO is normal

a The diagnosis of COPD is made with PFT: FEV1/FVC ratio remains < 70% after bronchodilator challenge (signifying irreversible obstruction).

Abbreviations: DLCO, diffusion lung capacity for carbon monoxide; HTN, hypertension; PFT, pulmonary function test.

3.4.1 General Principles of COPD Management

  • Smoking cessation (most important intervention that increases long-term survival rate).

  • Symptomatic control to improve quality of life.

  • Pulmonary rehabilitation program is recommended in patients with FEV1 < 50% of predicted. This has been shown to improve SOB and quality of life.

  • Pharmacological measures (see section below).

  • Treatment of acute exacerbation of COPD.

  • Long-term home oxygen therapy (increases long-term survival rate) in select patients.

  • Vaccination: flu vaccine is given every year. For pneumococcal vaccine give PPSV23 alone at diagnosis. After 5 years or at the age of 65 (whichever comes late) give PCV13 followed by PPSV23 (booster dose).

    19 All chronic lung diseases have this same schedule (e.g., asthma, bronchiectasis, interstitial lung disease, etc.)

Pharmacological measures to improve symptoms in COPD

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aLAMA is generally preferred because it is associated with reduced rate of exacerbation and it is also a once daily medication. Unlike asthma, in COPD inhaled steroids isn’t the 1st line therapy. In COPD, inhaled steroids have not been shown to alter long-term decline in FEV1; in-fact in old patients with advanced disease, inhaled steroids may actually increase the risk of pneumonia.

20 In COPD, inhaled steroids should not be used alone: use only in conjunction with either LABA or LAMA. In asthma, LABA should not be used alone: use only in conjunction with inhaled steroids.

bIn patients with evidence of reversibility of airway obstruction (asthmatic component), a combination regimen with LAMA or LABA + inhaled steroids might be preferred.

Abbreviations: NSIM, next step in management; SA BA/LABA, short-acting/long-acting B2 agonist; SAMA/LAMA, short-acting/long-acting muscarinic antagonist.

Other treatment modalities for refractory disease

Theophylline: It can be considered in patients with poor exercise tolerance despite triple therapy.

  • Coadministration of drugs that inhibit cytochrome enzyme pathway (e.g., erythromycin, H2 blockers, macrolides, quinolones, etc.) may result in high drug levels and increased toxicity.

  • Symptoms of toxicity are related to stimulation of various systems, as aminophylline is a stimulant drug. Symptoms are as follows:

    • Central nervous system stimulation: headache, insomnia, and seizures

    • Cardiovascular stimulation: arrhythmias

    • Gastrointestinal stimulation: nausea, vomiting, and diarrhea

Coadministration of cytochrome enzyme pathways inducers (e.g., phenobarbitals, rifampin) will result in low therapeutic levels

Roflumilast (oral phosphodiesterase inhibitor)

  • It is indicated in patients with severe COPD with chronic bronchitis and frequent exacerbations, despite triple therapy. It has been shown to reduce the frequency of exacerbations. exacerbations it is not used for patients with primary emphysema

  • It is contraindicated in patients with moderate to severe liver cirrhosis and depression

Chronic low-dose azithromycin therapy

Azithromycin also has anti-inflammatory effect. This can be considered, in-lieu of roflumilast in patients with frequent COPD exacerbations. Avoid this in patients with prolonged QT-interval.

Lung volume reduction surgery

In some carefully chosen patients with severe emphysematous disease who are good surgical candidates, this has been shown to improve quality of life and exercise capacity. Other alternative is placement of endobronchial valves.

Lung transplantation

Appropriate in patients with advanced COPD who are good surgical candidates, i.e., young patients with no major comorbidities. Active substance abuse is absolute contraindication.

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Dec 11, 2021 | Posted by in ENDOCRINOLOGY | Comments Off on 3. Pulmonology
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