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Asthma
Patients with asthma have increased nonspecific airway responsiveness that results in increased
sensitivity to inhaled bronchoconstrictive agents (such as methacholine) and airway obstruction that is
typically reversible. When patients with asthma are exposed to relevant allergens, they develop an earlyphase response that manifests 15 to 30 minutes after the exposure and resolves in 1 to 2 hours. Roughly
half of patients develop a late-phase response 3 to 8 hours following the exposure.
Epidemiology and Natural History
Asthma is one of the most common diseases, affecting 5% of the adult population in the United States.
Between 70% and 90% of patients with asthma have allergies demonstrated with skin testing and
confirmed by relevant history.
Although airway obstruction in asthma is reversible, there is a greater decline in lung function over time
among patients with asthma compared with healthy controls. This decline is more prominent in patients
who smoke.
Clinical Evaluation
Spirometry should be performed in patients with suspected asthma to confirm airway obstruction and
reversibility. Patients with suspected asthma who have normal spirometry should undergo a bronchial
challenge test to assess for airway hyperresponsiveness; a negative test generally excludes asthma.
The majority of patients with asthma have a personal and family history of allergies, and their exposure to
relevant allergens often provokes asthma symptoms. Other triggers include viral upper respiratory tract
infections, cold air, stress, and exercise. Asthma is generally worse at night. Most patients report
increased asthma symptoms at night or in the early morning at least once a month.
On initial evaluation of patients who are suspected of having asthma, spirometry should be performed to
confirm the diagnosis with demonstrated airway obstruction (low FEV 1/FVC ratio) and reversibility (12%
or greater improvement in FEV1 after administration of bronchodilators)
Asthma Syndromes
Occupational Asthma
Reactive Airways Dysfunction Syndrome
Virus-Induced Asthma
Cough-Variant Asthma
Gastroesophageal Reflux Disease and Asthma
Allergic Bronchopulmonary Aspergillosis
Exercise-Induced Bronchospasm
Vocal Cord Dysfunction
Aspirin-Sensitive Asthma
Occupational Asthma
Exposure to irritants, allergens, and sensitizing chemicals can be an important contributor to the
development or worsening of asthma. Therefore, any patient with asthma should be asked about workrelated exposures, keeping in mind that some exposures may be in the home environment. Patients with
occupational asthma report feeling better when away from the offending environment, such as on
weekends or vacations; however, symptoms may still occur even when away from the work environment
because of underlying airway hyperresponsiveness.
Avoidance of exposure to the offending agent (by changing jobs, changing the work environment, or
using protective equipment) is recommended. Patients with occupational asthma can show improvement
in lung function, symptoms, and airway hyperresponsiveness over time and can return to normal if they
have no further exposure to the offending agent.
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These different categories are associated with a stepwise approach to asthma management aimed at
reducing impairment and risk
Pharmacotherapy
Patients with asthma should be instructed on the use of inhalation devices at the initial clinic visit, and
their technique should be reviewed at subsequent visits.
Short-acting 2-agonists are the most effective bronchodilator medications available and have a rapid
onset of action.
Long-acting 2-agonists should be added to other asthma medications only after inhaled corticosteroid
therapy has been optimized.
Inhaled corticosteroids are the mainstay controller therapy for asthma.
Regular use of inhaled corticosteroids can result in systemic side effects; patients should be evaluated at
regular intervals for appropriateness of stepping down therapy to the lowest inhaled corticosteroid dose
consistent with adequate asthma control.
Management of Asthma Exacerbations
Increasing short-acting 2-agonists and consideration of a short course of systemic corticosteroids is
recommended to initiate treatment of exacerbation at home. If symptoms do not respond to these
measures, the patient should be evaluated in a clinical setting.
Spirometry and/or peak expiratory flow rate (PEFR) measurement is recommended. Patients with
moderate (PEFR 40%-69% of predicted or personal best) or severe (PEFR <40%) exacerbations should
be treated with frequent short-acting 2-agonists and systemic corticosteroids. In patients with severe
exacerbations, bronchodilator medications (short-acting 2-agonists and ipratropium) should be given by
nebulization, whereas in mild attacks an MDI with a holding chamber can be used. The intravenous route
is preferred for corticosteroids in severe attacks, whereas the oral route is used in milder cases. Most
patients should receive 5 to 7 days of oral corticosteroids (40 mg/d of prednisone) to ensure resolution
and reduce chances for recurrence. Pulse oximetry should be monitored, and supplemental oxygen should
be given to maintain saturation above 92%. Follow-up pulmonary function tests should be obtained in 1
hour; patients without significant improvement should be considered for hospitalization and patients with
a good response (PEFR >70%) that is sustained for 1 hour can be discharged.
Asthma and Pregnancy
Asthma is one of the most common medical problems that complicates pregnancy; better asthma control
is likely to reduce the risk to both mother and fetus.
During pregnancy, one third of patients have improvement in asthma control, another third have
worsening asthma, and another third have no change.
Short-acting 2-agonists (albuterol) are recommended for quick relief of asthma symptoms during
pregnancy, while inhaled corticosteroids are the mainstay controller medications. Among corticosteroids,
budesonide has the most safety data available during gestation and is recommended for use in pregnant
patients; however, patients who are already doing well on other inhaled corticosteroids can continue them
after they become pregnant because there has been no evidence of harm from the use of these
medications. The preferred second-line therapy is long-acting 2-agonists.
Alternative drugs that can be used during pregnancy include leukotriene receptor antagonists and
theophylline. Although systemic corticosteroids have been linked to a small risk of congenital
abnormalities, their use is recommended in patients with acute severe asthma. Left untreated, acute
asthma exacerbations can have serious morbidity for the mother and outcome of pregnancy.
Another means of assessing disease severity is the BODE (BMI, Obstruction, Dyspnea, Exercise) Index,
which is a composite disease marker that takes into account the systemic nature of COPD. The index
incorporates spirometry, MMRC scores, and other parameters and is useful in evaluating the risk for
hospitalization and estimating the long-term prognosis for patients with COPD. A higher score is
associated with worse outcomes. Pulmonologists also may use BODE scores in the assessment of patients
for lung transplantation. Patients with a BODE index score of 7 or higher will have a 4-year survival rate
of 20% or lower.
Ongoing Monitoring
Monitoring to adjust COPD therapy should focus on doses of medications, adherence to the regimen,
inhaler technique, effectiveness of symptom control, and the side effects of treatment. Periodic
spirometry should be performed to track a patient's lung function.
Exacerbation frequency and severity should be assessed with patient history and evaluation of symptoms.
Referral
Internists may consider referral to a pulmonary specialist in the presence of disease onset before 40 years
of age, a rapidly progressive course of disease, severe COPD despite optimal treatment, need for oxygen
therapy, onset of a comorbid condition, diagnostic uncertainty, symptoms disproportionate to the severity
of airway obstruction, confirmed or suspected 1-antitrypsin deficiency, a request for a second opinion,
possibility for lung transplantation or lung volume reduction surgery, very severe disease requiring
elective surgery that may impair respiratory function, or frequent exacerbations and persistent symptoms
despite adequate treatment
Management
The components of a COPD management plan are (1) identification and reduction of risk factors, (2)
assessment and monitoring of disease progression, (3) managing stable COPD, and (4) managing
exacerbations.
The frequency of exacerbations increases as the severity of COPD increases. Patients who experience
frequent exacerbations are also likely to have more symptoms, worsened health status, faster disease
progression, and an increased risk of death. To maximize outcomes, treatment regimens must be sustained
for the long term and reassessed periodically to monitor for efficacy and side effects.
Pharmacologic Therapy
Inhaled medications are central to the management of COPD; if a patient is not responding to therapy,
adherence should be verified and inhaler technique should be assessed before therapy is adjusted.
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COPD treatment consists of initiating monotherapy with a long-acting bronchodilator (including longacting 2-agonists or long-acting anticholinergic agents) in symptomatic patients with an FEV 1 less than
60% of predicted.
Inhaled corticosteroids should not be used alone for maintenance or rescue therapy in COPD.
Therapy with different combinations of long-acting 2-agonists, long-acting anticholinergic agents, and
inhaled corticosteroids is frequently used in patients with symptomatic COPD not controlled on
monotherapy; the optimal combination of medications and their safety and efficacy have not yet been
established.
Pneumococcal vaccination and annual influenza vaccination are recommended for all patients with
COPD.
Antibiotic Agents
Antibiotic therapy is most beneficial in treating infectious exacerbations of COPD that are characterized
by increases in dyspnea, sputum volume, and sputum purulence. Antibiotic therapy also is indicated
in patients with severe exacerbations of COPD who require mechanical ventilation, whether invasive or
noninvasive. Although the inciting factor of an exacerbation may be unknown, a fluoroquinolone such as
levofloxacin or the combination of a third-generation cephalosporin plus a macrolide antibiotic will
usually cover the most common bacterial pathogens (Haemophilus influenzae, Streptococcus pneumoniae,
and Moraxella catarrhalis as well as causes of atypical pneumonia). Even when the cause of the
exacerbation is viral, patients with COPD are often colonized with bacteria. Antibiotics in this setting
have been demonstrated to improve air flow, reduce mortality, and reduce treatment failure, especially in
patients experiencing more severe exacerbations. A number of meta-analyses and systematic reviews
support the use of antibiotic treatment for acute exacerbations of COPD.
Nonpharmacologic Therapy
Smoking cessation and oxygen therapy are the only interventions demonstrated to reduce COPD risk and
positively affect decline in pulmonary function; smoking cessation is the most important goal in the
management of COPD in patients who smoke, and it should be addressed at every visit.
Pulmonary rehabilitation (consisting of education, nutritional counseling, exercise training, assessment,
and follow-up) can be considered for all symptomatic patients with COPD who have an FEV 1 less than
50% of predicted.
Oxygen therapy is a major component of treatment for patients with very severe COPD and is indicated
for patients who have hypoxemia (arterial PO 2 55 mm Hg [7.3 kPa] or arterial oxygen saturation 88%).
Managing Exacerbations of COPD
Treatment of COPD exacerbations may involve additions or adjustments to bronchodilator therapy,
inhaled or systemic corticosteroid therapy, initiation of antibiotic treatment, possibly mechanical
ventilation, or hospitalization in severe exacerbations.
Home Management
Home care is increasingly common for the treatment of mild-to-moderate exacerbations of COPD as well
as for patients with end-stage disease.
Hospital Management
Risk of death from an exacerbation of COPD closely correlates with development of respiratory acidosis,
the presence of significant comorbidities, and requirement for ventilatory support. Patients with COPD
exacerbations should be hospitalized in the presence of underlying severe COPD, advanced patient age,
significant comorbidities, marked increase in intensity of symptoms, newly occurring arrhythmias,
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diagnostic uncertainty, insufficient home support, onset of new physical signs, or failure to respond
adequately to initial medical management. Admission of patients with severe exacerbations to
intermediate or special respiratory care units may be appropriate if personnel, skills, and equipment exist
to successfully identify and manage acute respiratory failure. Some patients may require direct admission
to the intensive care unit
Solid nodules that remain stable in size for 2 years on chest radiograph or CT scan are considered benign,
and no further follow-up is indicated; this is known as the 2-year stability rule.
Respiratory Failure
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Admission to the intensive care unit (ICU) for respiratory insufficiency is prompted by three basic
conditions: (1) hypoxemic respiratory failure; (2) ventilatory, or hypercapnic, respiratory failure; and (3)
impaired upper airway.
Hypoxemic Respiratory Failure
Positive end-expiratory pressure is the first-line approach to correcting shunt-associated hypoxemia in
patients with acute respiratory distress syndrome, but it is less applicable in the setting of focal disease.
The diagnosis of acute respiratory distress syndrome (ARDS) is predominantly made on clinical grounds,
and pulmonary artery catheters infrequently play a role in the diagnosis or management of ARDS.
Atelectasis is an important cause of hypoxemia in surgical and mechanically ventilated patients.
Acute hypoxemic respiratory failure is characterized by an abrupt, severe decline in oxyhemoglobin
saturation that does not readily correct with supplemental oxygen. Generally, the ambient air arterial PO 2
is 60 mm Hg (8.0 kPa) or less and the arterial PO 2/FIO2 is 200 mm Hg (26.6 kPa) or less; the arterial
PCO2 is typically normal or reduced. Rather, hypoxemia is reversed by application of positive endexpiratory pressure (PEEP) to the lung, which opens up, or recruits, flooded or collapsed alveoli.
Acute Respiratory Distress Syndrome
The Berlin criteria for the diagnosis of ARDS include:
(1) acute onset within 1 week of an apparent clinical insult or development and progression of respiratory
symptoms;
(2) bilateral opacities on chest imaging not explained by other pulmonary pathology (such as pleural
effusions, lung collapse, or nodules);
(3) respiratory failure not explained by heart failure or volume overload.
Mild ARDS is defined by an arterial PO2/FIO2 ratio between 201 and 300 mm Hg (26.7 and 39.9 kPa).
In moderate ARDS, the ratio is between 101 and 200 mm Hg (13.4 and 26.6 kPa), and
Severe ARDS is defined by a ratio of 100 mm Hg (13.3 kPa) or less.
All three categories require that measurement of the arterial PO 2/FIO2 ratio be performed with a PEEP
level of at least 5 cm H2O, which may be delivered noninvasively with CPAP in the mild ARDS group.
More than 60 disorders can precipitate ARDS by direct or indirect injury to the lung, but severe sepsis
from pneumonia or nonpulmonary sources constitutes the majority of cases. Deaths are primarily caused
by the underlying precipitant of lung injury or subsequent nosocomial infections rather than directly by
lung injury.
NonVentilator-Related Management
Mechanical ventilation is the primary supportive treatment in ARDS.
Many other therapies have been tried in ARDS, and most have shown an improvement in oxygenation but
not survival. Many therapies (inhaled vasodilators, prone positioning, occasionally corticosteroids) are
still used in the minority of patients with life-threatening hypoxemia despite aggressive ventilator support
even though there is no proven survival benefit.
Heart Failure
Patients with left ventricular systolic dysfunction are prone to acute cardiogenic pulmonary edema, but
the ejection fraction is normal in approximately half of patients admitted for heart failure. Diastolic
dysfunction, myocardial ischemia, hypertension, valve disease, and a variety of tachyarrhythmias are
important considerations in the absence of systolic failure. Regardless of the underlying cause, left-sided
heart failure can produce bilateral pulmonary infiltrates that are radiographically indistinguishable from
ARDS. Unlike ARDS, cardiogenic edema can rapidly improve with aggressive medical management, and
therefore early differentiation of the two disorders is important. Echocardiography is the primary means
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of diagnosing systolic and diastolic failure and valve disease. Evaluation for myocardial ischemia
includes measuring troponin levels and review of electrocardiograms for ischemic changes.
Electrocardiograms are also used to evaluate arrhythmias. B-type natriuretic peptide levels can be useful
in distinguishing cardiogenic from noncardiogenic edema in ambiguous cases, but they do not reliably
diagnose or exclude heart failure when evaluated in isolation.
Atelectasis
Chest physiotherapy, incentive spirometry, early mobilization, and continuous positive airway pressure
(CPAP) are commonly used in the perioperative period to prevent respiratory complications. Atelectasis is
also common in patients receiving invasive mechanical ventilation. Supine position, absence of
intermittent larger sigh breaths, and low tidal volumes predispose patients to bibasilar atelectasis. Mucus
plugging and right-mainstem intubation can precipitate lobar collapse.
Pneumonia
Lung consolidation due to pneumonia creates a physiologic shunt similar to cardiogenic and ARDSrelated edema. Pneumonia is the most common trigger for ARDS among nonhospitalized patients, and
differentiating bilateral pneumonia from pneumonia that has evolved into ARDS can be difficult.
Positioning the patient in the lateral decubitus position with the good lung dependent is a temporizing
measure that may reduce intrapulmonary shunt.
Ventilatory (Hypercapnic) Respiratory Failure
Ventilatory respiratory failure stems from inadequate alveolar ventilation relative to CO 2 production.
Causes of decreased alveolar ventilation fall into one of three basic categories: (1) decreased respiratory
drive, as seen with sedating drugs; (2) respiratory muscle weakness or excessive mechanical work of
breathing, as seen in neuromuscular disease and severe kyphoscoliosis; and (3) lung diseases in which
much of the inhaled gas does not participate in gas exchange. For instance, patients with COPD and
severe ARDS have increased dead space, or wasted ventilation, resulting from ongoing ventilation of
lung units that have injured capillary beds.
Ventilatory respiratory failure is characterized by hypoventilation and hypercapnia caused by excess
mechanical load, decreased respiratory drive, respiratory muscle weakness, increased dead-space
ventilation, and neuromuscular weakness.
Management of critically ill patients with neuromuscular weakness should consist of early identification
and treatment of ventilatory failure, minimizing aspiration risk, and assisting with airway clearance.
Increased work of breathing due to high airway resistance and air trapping, combined with increased
ventilatory demands, may lead to ventilatory failure in patients with obstructive lung disease.
The need for large amounts of supplemental oxygen in patients with exacerbations of COPD or asthma
should prompt consideration of alternative diagnoses.
Patients with acute upper airway obstruction should be closely monitored and there should be a low
threshold for intubation given the difficulty of endotracheal tube placement in this population.
Patients with a severe asthma exacerbation that does not respond to 1 hour of aggressive bronchodilator
therapy are candidates for admission to the intensive care unit.
A slightly elevated, or even normal, arterial PCO2 in a patient with an asthma exacerbation may indicate
impending respiratory arrest.
Noninvasive Mechanical Ventilation
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Noninvasive positive pressure ventilation (NPPV) consists of delivery of positive airway pressure breaths
without the use of an endotracheal tube or tracheostomy. NPPV settings include an inspiratory positive
airway pressure (IPAP) and an end-expiratory positive airway pressure (EPAP).
Indications
Obstructive Lung Disease
Noninvasive positive pressure ventilation is the standard of care for managing moderate to severe COPD
exacerbations.
Cardiogenic Pulmonary Edema
Several randomized trials indicate that NPPV and CPAP improve dyspnea and gas exchange in patients
with respiratory failure due to acute cardiogenic pulmonary edema.
Immunocompromised Patients
There is a strong rationale for avoiding intubation in immunocompromised patients given their increased
risk of nosocomial infections, including ventilator-associated pneumonia.
Following Extubation
NPPV can be used in various ways to facilitate weaning from invasive mechanical ventilation. Taken
together, the evidence suggests that the use of NPPV in patients in whom a trial of extubation has failed
should be limited primarily to those with chronic lung disease and hypercapnia.
Other Populations with Hypoxemic Respiratory Failure
CPAP reduces the need for intubation in patients with hypoxemic respiratory failure complicating
abdominal surgery as well as following lung resection, presumably by reducing atelectasis.
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