Managing COPD with Bronchodilators

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Questions and Answers

What is recommended for patients with persistent breathlessness or exercise limitation on bronchodilator monotherapy?

Use of two long-acting bronchodilators (correct)

Use of a single long-acting bronchodilator

Use of a short-acting bronchodilator

Use of bronchodilator and corticosteroids

What is the recommended escalation for patients with persistent exacerbations on bronchodilator monotherapy and blood eosinophil count ≥ 300 cells/μL?

Addition of roflumilast

Escalation to LABA+LAMA+ICS (correct)

Escalation to LABA+LAMA

Addition of azithromycin

What is the next step for patients on LABA+LAMA who still have exacerbations and have eosinophil counts < 100 cells/μL?

Remain on LABA+LAMA

Switch to monotherapy

Escalate to LABA+LAMA+ICS

Consider adding roflumilast or azithromycin (correct)

Which condition must be met to consider adding roflumilast?

FEV1 < 50% predicted and chronic bronchitis Signup and view all the answers

When is adding azithromycin particularly considered?

In patients who are not current smokers Signup and view all the answers

What is the escalation recommendation for patients with persistent exacerbations on bronchodilator monotherapy and blood eosinophil count < 300 cells/μL?

Escalation to LABA+LAMA Signup and view all the answers

What is the main purpose of short-acting bronchodilators for patients with COPD?

To manage symptoms as rescue or as-needed therapy Signup and view all the answers

What is a characteristic shared by short-acting β2-agonists and short-acting muscarinic antagonists?

Both have a relatively rapid onset of action Signup and view all the answers

What is the preferred route of administration for short-acting β2-agonists?

Inhalation Signup and view all the answers

What is a reasonable step if a patient does not achieve adequate symptom control with one short-acting bronchodilator?

Adding a SAMA to a SABA Signup and view all the answers

What are the two types of short-acting bronchodilators mentioned in the text?

Short-acting β2-agonists and short-acting muscarinic antagonists Signup and view all the answers

What are the two SABA options mentioned in the text?

Albuterol and levalbuterol Signup and view all the answers

What is a common initial side effect of skeletal muscle disturbances?

Tremors Signup and view all the answers

Which group of patients are more sensitive to rhythm disturbances?

Older patients Signup and view all the answers

What is a characteristic difference between ipratropium and albuterol?

Slower onset of action for ipratropium Signup and view all the answers

What is a common complaint among patients using ipratropium bromide?

Dry mouth Signup and view all the answers

What is a potential reason ipratropium may be less suitable for as-needed use?

It has a slower onset Signup and view all the answers

Which type of medication is available as a long-acting form for bronchodilator therapy?

Long-acting β2-agonist (LABA) Signup and view all the answers

How is the starting dose for any of the long-acting bronchodilators determined?

It is the effective and recommended dose from the outset Signup and view all the answers

What is a characteristic of the LABA formoterol in terms of onset of action?

It has an onset of action similar to albuterol Signup and view all the answers

Which of the following is NOT true about long-acting bronchodilator therapy?

Formoterol's onset of action is different from albuterol Signup and view all the answers

Which class of drugs does the muscarinic antagonist belong to in the context of bronchodilator therapy?

Long-acting muscarinic antagonists Signup and view all the answers

Why should chronic systemic corticosteroids be avoided in COPD patients?

They offer questionable benefits. Signup and view all the answers

What is the primary function of roflumilast in COPD treatment?

To relax airway smooth muscle Signup and view all the answers

For which COPD patients is roflumilast particularly recommended?

Those with recurrent exacerbations despite triple inhalation therapy Signup and view all the answers

What is one acceptable use of short-term systemic corticosteroids in COPD patients?

For treating acute exacerbations Signup and view all the answers

Which therapy combination is recommended over ICS monotherapy for COPD patients?

Combination therapy including ICS Signup and view all the answers

What is a possible consequence of chronic azithromycin use?

Colonization with macrolide resistant bacteria and hearing deficits Signup and view all the answers

What is the definition of a COPD exacerbation?

A change in the patient’s baseline symptoms sufficient to warrant a change in management Signup and view all the answers

When is adding azithromycin particularly considered in COPD patients?

For patients with recurrent exacerbations despite optimal therapy Signup and view all the answers

What is the classification of a COPD exacerbation that requires hospitalization or emergency department visits?

Severe Signup and view all the answers

What is a precaution listed in the azithromycin product labeling?

QT prolongation Signup and view all the answers

What is the primary goal of treatment for COPD exacerbations?

To minimize the negative consequences of the acute exacerbation and prevent future exacerbations Signup and view all the answers

What type of ventilation may be necessary for patients failing noninvasive positive-pressure ventilation (NPPV)?

Intubation and mechanical ventilation Signup and view all the answers

What are the three classes of medications commonly used for COPD exacerbations?

Bronchodilators, corticosteroids, and antibiotics Signup and view all the answers

What is the purpose of providing oxygen therapy for patients with COPD?

To treat hypoxemia Signup and view all the answers

What is the role of noninvasive positive-pressure ventilation (NPPV) in COPD treatment?

To provide ventilatory support with oxygen Signup and view all the answers

What is the preferred initial bronchodilator for acute treatment of a COPD exacerbation?

Inhaled SABAs Signup and view all the answers

What is the reason for not recommending methylxanthines for COPD treatment?

They have increased side effect profiles Signup and view all the answers

Which of the following methods of administration has equal efficacy in delivering bronchodilators?

MDI, DPI, or nebulization Signup and view all the answers

When may nebulization be considered for delivering bronchodilators?

For patients with severe dyspnea who are unable to hold their breath after actuation of an MDI Signup and view all the answers

What may be added to SABAs if symptoms persist despite increased doses of β2-agonists?

Muscarinic antagonists Signup and view all the answers

What is the recommended duration for corticosteroid therapy with prednisone in COPD exacerbations?

5 days Signup and view all the answers

When should antibiotics be initiated for a patient with COPD exacerbation?

If the patient presents with increased sputum purulence and requires mechanical ventilation Signup and view all the answers

What is considered a cardinal symptom for initiating antibiotics in COPD exacerbation?

Worsening dyspnea Signup and view all the answers

Which clinical situation does NOT indicate the need to initiate antibiotics in COPD exacerbation?

Presence of one cardinal symptom without any mechanical ventilation Signup and view all the answers

Streptococcus pneumoniae is most commonly associated with which condition?

COPD exacerbations Signup and view all the answers

Which type of medication is typically used as an initial empirical treatment for patients?

Aminopenicillin with clavulanic acid Signup and view all the answers

What is the recommended duration for antimicrobial therapy in the treatment of exacerbations?

5-7 days Signup and view all the answers

Which parameter should be assessed annually in chronic stable COPD?

Pulmonary function tests Signup and view all the answers

Which additional assessments are necessary during more severe exacerbations of COPD?

ABG and SaO2 Signup and view all the answers

When is hospitalization considered for patients not responding to initial treatment of exacerbations?

If the patient's condition deteriorates or does not improve as anticipated Signup and view all the answers

What is the primary mode of transmission for Mycobacterium tuberculosis?

Coughing or other aerosol-producing activities Signup and view all the answers

Which group of individuals is at the highest risk for progressing from TB infection to active TB disease?

HIV-infected individuals Signup and view all the answers

What is miliary TB characterized by?

Widely disseminated disease and granuloma formation Signup and view all the answers

How many new cases of TB were reported in 2019?

10 million Signup and view all the answers

Which statement reflects an important risk factor for progressing to active TB?

Being co-infected with HIV Signup and view all the answers

What is the typical symptom onset of patients with TB?

Gradual Signup and view all the answers

What is the primary purpose of the tuberculin skin test?

To screen for tuberculous infection Signup and view all the answers

What is the characteristic of patients with HIV and TB?

They have a higher incidence of extrapulmonary TB Signup and view all the answers

What is the recommended method for isolating M. tuberculosis?

Daily sputum collection over 3 consecutive days Signup and view all the answers

What is the purpose of tests that measure the release of interferon-γ in the patient's blood?

To identify M. tuberculosis Signup and view all the answers

What is the typical presentation of extrapulmonary TB?

Slowly progressive decline of organ function with low-grade fever Signup and view all the answers

What is one of the primary goals of tuberculosis (TB) treatment?

Achieving a noninfectious state in the patient Signup and view all the answers

Which strategy is considered the standard of care to ensure completion of TB treatment?

Directly observed therapy (DOT) by a healthcare worker Signup and view all the answers

How long is drug treatment continued for cases of multidrug-resistant TB (MDR-TB)?

18-24 months Signup and view all the answers

What is the minimum number of drugs that must be used simultaneously in TB drug treatment?

Two drugs Signup and view all the answers

In which situation might surgery be considered necessary during TB treatment?

To remove destroyed lung tissue or extrapulmonary lesions Signup and view all the answers

Why is adherence to the TB treatment regimen important?

To prevent the development of resistance Signup and view all the answers

What is the recommended treatment regimen for latent tuberculosis infection (LTBI) in otherwise healthy patients aged 12 years or older?

3 months of once weekly isoniazid plus rifapentine Signup and view all the answers

What should be provided to pregnant women, alcoholics, and patients with poor diets who are treated with isoniazid?

Pyridoxine, 10–50 mg daily Signup and view all the answers

What is the primary goal of chemoprophylaxis in patients with latent tuberculosis infection?

To reduce the risk of progression to active disease Signup and view all the answers

How many treatment regimens are recommended for latent tuberculosis infection (LTBI)?

3 Signup and view all the answers

What is the recommended duration of treatment for latent tuberculosis infection (LTBI) with isoniazid plus rifapentine?

3 months Signup and view all the answers

What combination of drugs is recommended for the first 2 months of standard TB treatment?

Isoniazid, rifampin, pyrazinamide, and ethambutol Signup and view all the answers

What should be done prior to initiating therapy for all patients with active TB?

Send appropriate samples for culture and susceptibility testing Signup and view all the answers

Under what condition can ethambutol be stopped during TB treatment?

When susceptibility to isoniazid, rifampin, and pyrazinamide is confirmed Signup and view all the answers

Why is it essential to know the previous drugs used for retreatment of TB?

To prevent reusing ineffective drugs Signup and view all the answers

What is the total duration of the standard TB treatment regimen?

6 months Signup and view all the answers

What is a critical aspect to avoid in the treatment of drug-resistant TB?

Monotherapy Signup and view all the answers

Which group of patients should drug resistance be suspected in if they still have positive cultures after a specific duration of therapy?

2-4 months Signup and view all the answers

Which patients are at higher risk of drug-resistant TB due to geographic location?

South Africa Signup and view all the answers

In the management of MDR-TB, what is typically not provided due to the varied nature of the condition?

Standard regimen Signup and view all the answers

What is a common characteristic among certain patients that warrants suspicion of drug resistance?

Institutionalization Signup and view all the answers

Which drug used for CNS TB readily penetrates the cerebrospinal fluid?

Isoniazid Signup and view all the answers

How long are patients with CNS TB often treated?

9-12 months Signup and view all the answers

Which of the following TB types is typically treated for 9 months, occasionally with surgical debridement?

TB of the bone Signup and view all the answers

Which treatment regimen is usually administered to pregnant women with TB?

Isoniazid, rifampin, and ethambutol for 9 months Signup and view all the answers

Why should women with TB be cautioned against becoming pregnant?

The disease poses a risk to the fetus as well as to the mother Signup and view all the answers

Which supplement is particularly important for pregnant women undergoing TB treatment?

Vitamin B Signup and view all the answers

What is a significant concern with the use of Ethionamide during pregnancy?

Associated with premature delivery and congenital deformities Signup and view all the answers

Which medication typically requires a reduction in dosing frequency from daily to three times weekly in patients with renal failure?

Pyrazinamide and ethambutol Signup and view all the answers

What is the most serious problem with TB therapy?

Nonadherence to the prescribed regimen Signup and view all the answers

Which laboratory tests should be performed at baseline and periodically during TB therapy?

Blood urea nitrogen, serum creatinine, liver enzymes, and complete blood count Signup and view all the answers

What condition should suspect hepatotoxicity in TB patients?

Transaminases exceed five times the upper limit of normal or total bilirubin exceeds 3 mg/dL Signup and view all the answers

Which medication should be avoided during pregnancy and nursing?

Fluoroquinolones Signup and view all the answers

What characterizes anemia?

A decrease in hemoglobin or red blood cells Signup and view all the answers

What is the World Health Organization's definition of anemia in men?

Hb less than 13 g/dL Signup and view all the answers

What is the primary effect of anemia on the body?

Decreased oxygen-carrying capacity of blood Signup and view all the answers

What is the difference in the World Health Organization's definition of anemia between men and women?

1 g/dL higher in men Signup and view all the answers

What is a common laboratory value used to diagnose anemia?

Hemoglobin level Signup and view all the answers

Which deficiency is most commonly associated with macrocytic cells?

Vitamin B12 deficiency Signup and view all the answers

What is a characteristic marker for iron-deficiency anemia (IDA)?

Decreased transferrin saturation Signup and view all the answers

Which condition is typically associated with microcytic cells?

Iron deficiency Signup and view all the answers

Which deficiency anemia is characterized by decreased dietary intake and malabsorption syndromes?

Folic acid-deficiency anemia Signup and view all the answers

What may be a cause of iron-deficiency anemia aside from dietary intake and blood loss?

Pregnancy Signup and view all the answers

What is the primary cause of pernicious anemia?

Deficiency of intrinsic factor Signup and view all the answers

Which condition is NOT a cause of folic acid–deficiency anemia?

Iron deficiency Signup and view all the answers

How can phenytoin cause anemia?

Reducing folate absorption Signup and view all the answers

Which of the following is a characteristic of anemia of inflammation (AI)?

Associated with release of proinflammatory cytokines Signup and view all the answers

What differentiates anemia of inflammation (AI) from iron deficiency anemia (IDA)?

Normal or increased serum ferritin concentration Signup and view all the answers

What is the earliest and most sensitive laboratory change for iron deficiency anemia?

Decreased serum ferritin Signup and view all the answers

What is a characteristic of chronic anemia?

Weakness, fatigue, and headache Signup and view all the answers

What is a possible neurologic effect of vitamin B12 deficiency?

Numbness and paraesthesia Signup and view all the answers

What is the primary reason for rapid diagnosis of anemia?

Anemia is often a sign of underlying pathology Signup and view all the answers

What is a characteristic of iron deficiency anemia?

Glossal pain and smooth tongue Signup and view all the answers

What is the initial evaluation of anemia?

Complete blood cell count and reticulocyte index Signup and view all the answers

What distinguishes anemia of inflammation (AI) from iron-deficiency anemia (IDA) in serum iron and ferritin levels?

Serum ferritin is normal or increased in AI but decreased in IDA. Signup and view all the answers

What is the recommended dosage regimen for oral iron therapy in iron-deficiency anemia?

150-200 mg elemental iron in two to three divided doses per day. Signup and view all the answers

From which sources is iron best absorbed when taken orally?

Meat, fish, and poultry Signup and view all the answers

When should parenteral iron be considered for patients with iron-deficiency anemia?

For patients who experience severe side effects with oral iron Signup and view all the answers

What is a common characteristic of parenteral iron preparations such as iron dextran and iron sucrose?

They have similar efficacy but different pharmacokinetics. Signup and view all the answers

What is one of the goals of treating iron-deficiency anemia?

To restore normal function and quality of life Signup and view all the answers

What is the recommended treatment for folic acid–deficiency anemia?

Daily oral folic acid administration for 4 months Signup and view all the answers

What is the recommended duration of vitamin B12 supplementation in patients with pernicious anemia?

For life Signup and view all the answers

What is the recommended treatment approach for anemia of inflammation?

Correcting reversible causes Signup and view all the answers

Why is parenteral therapy preferred over oral therapy in some cases of vitamin B12 deficiency anemia?

It has a faster onset of action Signup and view all the answers

What is the recommended approach to iron therapy in anemia of inflammation?

Reserve iron therapy for established IDA Signup and view all the answers

What is the threshold for considering RBC transfusions in anemia of inflammation?

Hb of 7-8 g/dL Signup and view all the answers

What can be considered in patients with AI in addition to iron, cobalamin, and folic acid supplementation?

ESAs Signup and view all the answers

What is associated with increased mortality and cardiovascular events during ESA therapy?

Rise of greater than 1 g/dL every 2 weeks Signup and view all the answers

What should be monitored during ESA therapy?

Hb Signup and view all the answers

What is the recommended dose of ferrous sulfate for infants aged 9–12 months?

3–6 mg/kg/day Signup and view all the answers

How long should iron therapy continue in responders to replace storage iron pools?

Up to 12 months Signup and view all the answers

What is the characteristic of response to oral iron therapy in IDA?

Increase in Hb seen at 2 weeks Signup and view all the answers

Study Notes

Treatment of Persistent Breathlessness or Exercise Limitation

For patients with persistent breathlessness or exercise limitation on bronchodilator monotherapy, using two long-acting bronchodilators is recommended.

Managing Exacerbations

For patients with persistent exacerbations on bronchodilator monotherapy:
- If blood eosinophil count ≥ 300 cells/μL, escalation to LABA+LAMA+ICS may be considered.
- If blood eosinophil count < 300 cells/μL, escalation to LABA+LAMA is recommended.

Escalation Options for Persistent Exacerbations

In patients on LABA+LAMA and still having exacerbations:
- If eosinophil counts ≥ 100 cells/ml, escalation to LABA+LAMA+ICS may be considered.
In patients on LABA+LAMA and eosinophil counts < 100 cells/μL who still have exacerbations, or patients treated with LABA+LAMA+ICS and still having exacerbations:
- Adding roflumilast may be considered in patients with an FEV1 < 50% predicted and chronic bronchitis.
- Adding azithromycin may be considered, especially in those who are not current smokers.

Treatment of COPD Symptoms

For patients with occasional symptoms, either short- or long-acting bronchodilators are recommended initially.
Short-acting bronchodilators are recommended for all patients as rescue or as-needed therapy to manage symptoms, regardless of category (A-E).

Short-Acting Bronchodilator Options

Short-acting β2-agonists (SABAs) and short-acting muscarinic antagonists (SAMAs) are both effective options.
Both SABAs and SAMAs have a rapid onset of action, relieve symptoms to a similar degree, and improve exercise tolerance and lung function.

Limitations of Short-Acting Bronchodilators

Short-acting bronchodilators do not reduce the frequency or severity of COPD exacerbations.

Combining Short-Acting Bronchodilators

If a patient does not achieve adequate symptom control with one agent, combining a SABA with a SAMA is a reasonable approach.

SABA Options and Administration

Albuterol and levalbuterol are SABA options.
Inhalation is the preferred route for SABAs.
Administration via metered-dose or dry powder inhalers (MDIs, DPIs) is at least as effective as nebulization therapy and is more convenient and less costly.

Adverse Effects

Rhythm disturbances can occur in predisposed patients, but are rare
Skeletal muscle tremors can occur initially, but generally subside as tolerance develops
Older patients may be more sensitive to the medication, experiencing palpitations, tremors, and “jittery” feelings

Ipratropium Bromide

Characteristics

Ipratropium bromide is the most commonly prescribed SAMA
Improvements in pulmonary function are similar to inhaled SABAs

Pharmacokinetics

Slower onset of action (15–20 minutes) compared to albuterol (5 minutes)
More prolonged effect compared to albuterol

Clinical Use

May be less suitable for as-needed use due to slower onset, but is often prescribed in this manner

Side Effects

Dry mouth is a frequent patient complaint
Nausea is a frequent patient complaint
Metallic taste is an occasional patient complaint

Long-Acting Bronchodilators

Long-acting bronchodilators can be administered as either an inhaled long-acting β2-agonist (LABA) or muscarinic antagonist (LAMA).
There is no dose titration for LABA or LAMA, meaning the starting dose is the effective and recommended dose for all patients.

LABA Formoterol

Formoterol has an onset of action similar to albuterol.

Corticosteroids in COPD Treatment

Combination therapy with ICS is beneficial for patients with COPD, while ICS monotherapy is not recommended.
Short-term systemic corticosteroids may be used for acute exacerbations, but chronic systemic corticosteroids should be avoided due to high risk of toxicity and questionable benefits.

Roflumilast in COPD Treatment

Roflumilast is a phosphodiesterase 4 (PDE4) inhibitor that relaxes airway smooth muscle.
Roflumilast is recommended for patients with recurrent exacerbations despite treatment with triple inhalation therapy (LAMA/LABA/ICS) or dual therapy (LAMA/LABA) who are not candidates for ICS (eosinophil count <100cells/μL).

Chronic Azithromycin in COPD

Chronic azithromycin is associated with a lower rate of COPD exacerbations, but also with increased colonization of macrolide-resistant bacteria and hearing deficits.
Azithromycin product labeling includes a precaution about QT prolongation.

COPD Exacerbations

A COPD exacerbation is defined as a change in a patient's baseline symptoms, such as worsening dyspnea, increased sputum volume, or increased sputum purulence, that warrants a change in management.
Classification of COPD exacerbations:
- Mild: managed with short-acting (SA) bronchodilators only
- Moderate: managed with SA bronchodilators plus antibiotics and/or oral corticosteroids
- Severe: requires hospitalization or emergency department (ED) visits

Guidelines for Chronic Azithromycin Use

Current guidelines recommend considering chronic azithromycin only for patients with recurrent exacerbations despite optimal therapy, particularly in non-smokers.

Goals of Treatment

Minimize negative consequences of acute exacerbation: reduce symptoms, prevent hospitalization, shorten hospital stay, prevent acute respiratory failure or death
Prevent future exacerbations

Nonpharmacologic Therapy

Provide oxygen therapy for patients with significant hypoxemia
Use noninvasive positive-pressure ventilation (NPPV) for ventilatory support with oxygen using a face or nasal mask without endotracheal intubation
Consider intubation and mechanical ventilation for patients failing NPPV or who are poor candidates for NPPV

Pharmacologic Therapy

Three classes of medications commonly used for COPD exacerbations: bronchodilators, corticosteroids, and antibiotics

Bronchodilators for COPD Exacerbation

Inhaled SABAs are recommended as the initial bronchodilators for acute treatment of COPD exacerbation due to their rapid onset of action.
Muscarinic antagonists can be added to SABAs if symptoms persist despite increased doses of β2-agonists.

Administration of Bronchodilators

Bronchodilators can be administered via MDI, DPI, or nebulization with equal efficacy.
Nebulization is recommended for patients with severe dyspnea who are unable to hold their breath after actuation of an MDI.

Methylxanthines

Methylxanthines are not recommended for COPD exacerbation due to their increased side effect profiles.
I.V methylxanthines (theophylline or aminophylline) are not recommended due to significant side effects.

Corticosteroids in COPD Exacerbations

The optimal corticosteroid dose and duration are unknown, but 40 mg of prednisone orally daily for 5 days is effective for many patients.

Antimicrobial Therapy in COPD Exacerbations

Antibiotics should be initiated in patients with: • Three cardinal symptoms of acute exacerbation: worsening dyspnea, increased sputum volume, or increased sputum purulence. • Two cardinal symptoms, as long as one is increased sputum purulence. • Mechanical ventilation requirement, regardless of symptoms.
The most common pathogens in COPD exacerbations include Streptococcus pneumoniae.

Empirical Treatment of COPD Exacerbations

Initial empirical treatment typically involves an aminopenicillin with clavulanic acid, macrolide, tetracycline, or quinolone (in selected patients).

Duration of Antimicrobial Therapy

Continue antimicrobial therapy for at least 5–7 days.

Monitoring Patient Response

If the patient deteriorates or fails to improve as anticipated, hospitalization may be necessary, and more aggressive efforts should be made to identify responsible pathogens.

Evaluating Therapeutic Outcomes

In Chronic Stable COPD

Assess pulmonary function tests annually and with any treatment additions or discontinuations.

In Acute Exacerbations of COPD

Monitor white blood cell count, vital signs, chest x-ray, and changes in frequency of dyspnea, sputum volume, and sputum purulence at the onset and throughout treatment.

In More Severe Exacerbations

Monitor ABG and SaO2 in addition to the above.

Tuberculosis (TB) Basics

TB is a communicable infectious disease caused by Mycobacterium tuberculosis.
TB can produce silent, latent infection, as well as progressive, active disease.

Epidemiology of TB

In 2019, there were approximately 10 million new cases of TB and 1.2 million deaths from TB reported.

Transmission and Risk Factors

M. tuberculosis is transmitted from person to person by coughing or other activities that cause the organism to be aerosolized.
Close contacts of TB patients are most likely to become infected.
Human immunodeficiency virus (HIV) is the most important risk factor for progressing to active TB.
An HIV-infected individual with TB infection is over 100-fold more likely to develop active disease than an HIV-seronegative patient.

Complications of TB

A massive inoculum of organisms may be introduced into the bloodstream, causing widely disseminated disease and granuloma formation known as miliary TB.

Clinical Presentation of TB

Typical symptoms of TB include cough, weight loss, fatigue, fever, and night sweats, with gradual symptom onset.
Frank hemoptysis is a late-stage symptom, but can occur earlier in the disease course.

Diagnosis of TB

Sputum smear and chest radiograph are essential for TB diagnosis.
Extrapulmonary TB clinical features vary depending on the affected organ system, but typically involve a slow decline in organ function, low-grade fever, and constitutional symptoms.

TB in HIV-Positive Patients

HIV-positive patients may have an atypical TB presentation, with fewer skin test positives and fever.
They have a higher incidence of extrapulmonary TB and are more likely to present with progressive primary disease.

Screening and Testing for TB

The tuberculin skin test, using purified protein derivative (PPD), is the most widely used screening method for tuberculous infection.
To isolate M. tuberculosis, attempts should be made to collect daily sputum samples over 3 consecutive days.
Interferon-γ release assays can provide quick and specific results for identifying M. tuberculosis in the patient's blood in response to TB antigens.

Goals of Treatment

Rapid identification of new TB cases
Initiation of specific anti-TB treatment
Eradication of M.tuberculosis infection
Achievement of a noninfectious state in the patient, ending isolation
Prevention of resistance development
Patient adherence to treatment regimen
Quick cure of patient (at least 6 months)

Isolation and Treatment

Active disease patients should be isolated to prevent disease spread
Drug treatment is the cornerstone of TB management
Minimum of two drugs, generally three or four, must be used simultaneously
Directly observed therapy (DOT) by a healthcare worker ensures treatment completion, considered the standard of care
Treatment duration: at least 6 months, 18-24 months for multidrug-resistant TB (MDR-TB)

Additional Interventions

Surgery may be necessary to remove destroyed lung tissue, space-occupying lesions, and some extrapulmonary lesions

Pharmacologic Therapy for Latent Tuberculosis Infection

Chemoprophylaxis is recommended to reduce the risk of progression to active disease in patients with latent tuberculosis infection (LTBI).
Three treatment regimens are recommended for LTBI:
- 3 months of once weekly isoniazid plus rifapentine
- 4 months of daily rifampin
- 3 months of daily isoniazid plus rifampin
The Centers for Disease Control and Prevention (CDC) recommends the 12-week isoniazid/rifapentine regimen as an equal alternative to 9 months of daily isoniazid for treating LTBI in otherwise healthy patients aged 12 years or older with a higher likelihood of developing active TB.
Special considerations for patient populations:
- Pregnant women, alcoholics, and patients with poor diets treated with isoniazid should receive pyridoxine (10-50 mg daily) to reduce the incidence of CNS effects or peripheral neuropathies.

Treatment of Culture-Positive Pulmonary TB

Options for treatment of culture-positive pulmonary TB caused by drug-susceptible organisms are listed in Table 1.

Standard TB Treatment Regimen

The standard treatment regimen consists of isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months, followed by isoniazid and rifampin for 4 months.
Total treatment duration is 6 months.
Ethambutol can be stopped if the patient is susceptible to isoniazid, rifampin, and pyrazinamide.

Initial Therapy and Drug Selection

Appropriate samples should be sent for culture and susceptibility testing prior to initiating therapy for all patients with active TB.
The data from these tests should guide the initial drug selection for the new patient.

Retreatment of TB

If the patient is being evaluated for the retreatment of TB, it is essential to know what drugs were used previously and for how long.

Managing Drug Resistance

When dealing with drug-resistant organisms, the goal is to introduce two or more active agents that the patient has not received previously to combat the resistance.

Avoiding Monotherapy

It is crucial to avoid monotherapy or adding only a single drug to a failing regimen to prevent further resistance.

Suspecting Drug Resistance

Drug resistance should be suspected in patients who have received prior therapy for TB.
Geographic areas with high prevalence of resistance include South Africa, Mexico, Southeast Asia, the Baltic countries, and the former Soviet states.
Patients with high-risk factors, such as being homeless, institutionalized, IV drug abusers, and/or infected with HIV, should be suspected of having drug resistance.
Patients who still have acid-fast bacilli–positive sputum smears after 2 months of therapy may have drug resistance.
Patients who still have positive cultures after 2–4 months of therapy may indicate drug resistance.
Patients who fail therapy or relapse after retreatment may have drug resistance.
Patients known to be exposed to MDR-TB cases should be suspected of having drug resistance.

MDR-TB

There is no standard regimen for MDR-TB.

Special Populations

Tuberculous Meningitis and Extrapulmonary Disease

Isoniazid, pyrazinamide, ethionamide, cycloserine, and linezolid penetrate the cerebrospinal fluid readily.
Patients with CNS TB require longer treatment periods, typically 9-12 months.
Extrapulmonary TB of soft tissues can be treated with conventional regimens.
TB of the bone is typically treated for 9 months, with occasional surgical debridement.

Children

Children with TB can be treated with regimens similar to those used in adults.
Treatment duration may be extended to 9 months in some cases.
Pediatric doses of drugs should be used.

Pregnant Women

The standard treatment for pregnant women is 9 months of isoniazid, rifampin, and ethambutol.
Pregnant women with TB should be cautioned against becoming pregnant again, as the disease poses risks to the fetus and mother.
Isoniazid and ethambutol are relatively safe during pregnancy.
Supplementation with B vitamins is crucial during pregnancy.
Rifampin has been linked to rare birth defects, including limb reduction and CNS lesions, although these are occasionally severe.

Pregnancy and TB Medications

Pyrazinamide: limited studies, but anecdotal evidence suggests it may be safe during pregnancy
Ethionamide: associated with premature delivery, congenital deformities, and Down syndrome, and thus not recommended during pregnancy
Cycloserine: not recommended during pregnancy
Fluoroquinolones: should be avoided during pregnancy and nursing

Renal Failure and TB Medications

Isoniazid and rifampin: do not require dose modifications in renal failure
Pyrazinamide and ethambutol: typically require a reduction in dosing frequency from daily to three times weekly in renal failure

Evaluation of Therapeutic Outcomes

Nonadherence to the prescribed regimen is the most serious problem with TB therapy
Directly Observed Therapy (DOT) is the most effective way to ensure adherence
Baseline and periodic monitoring of blood urea nitrogen, serum creatinine, aspartate transaminase or alanine transaminase, and complete blood count is recommended
Hepatotoxicity should be suspected if transaminases exceed five times the upper limit of normal or total bilirubin exceeds 3 mg/dL, and the offending agent(s) should be discontinued and alternatives selected

Anemia Definition and Diagnosis

Anemia is a group of diseases characterized by a decrease in hemoglobin (Hb) or the volume of red blood cells (RBCs), leading to decreased oxygen-carrying capacity of blood.
The World Health Organization (WHO) defines anemia as:
- Hemoglobin (Hb) less than 13 g/dL in men
- Hemoglobin (Hb) less than 12 g/dL in women

Morphologic Classifications of Anemia

Based on cell size, anemia can be classified into macrocytic, microcytic, or normocytic anemia

Macrocytic Anemia

Characterized by larger than normal red blood cells
Associated with deficiencies of vitamin B12 or folic acid

Microcytic Anemia

Characterized by smaller than normal red blood cells
Associated with iron deficiency

Normocytic Anemia

Characterized by normal-sized red blood cells
May be associated with recent blood loss or chronic disease

Iron-Deficiency Anemia (IDA)

Characterized by decreased levels of ferritin (most sensitive marker) and serum iron, and decreased transferrin saturation
Can be caused by:
- Inadequate dietary intake
- Inadequate gastrointestinal (GI) absorption
- Increased iron demand (e.g., pregnancy)
- Blood loss
- Chronic diseases

Vitamin B12- and Folic Acid-Deficiency Anemias

Characterized by macrocytic anemia
Can be caused by:
- Inadequate dietary intake
- Malabsorption syndromes
- Inadequate utilization

Vitamin Deficiency Anemia

Deficiency of intrinsic factor leads to decreased absorption of vitamin B12, causing pernicious anemia.

Folic Acid Deficiency Anemia

Folic acid deficiency can be caused by hyperutilization due to:
- Pregnancy
- Hemolytic anemia
- Malignancy
- Chronic inflammatory disorders
- Long-term dialysis
- Growth spurt
Certain drugs can cause anemia by:
- Reducing absorption of folate (e.g., phenytoin)
- Folate antagonism (e.g., methotrexate)

Anemia of Inflammation (AI)

Anemia of inflammation (AI) is a newer term encompassing both anemia of chronic disease and anemia of critical illness.
AI is typically associated with:
- Malignant processes
- Infectious processes
- Inflammatory processes
- Tissue injury
- Conditions releasing proinflammatory cytokines
Serum iron levels are decreased in AI, but unlike iron deficiency anemia (IDA), serum ferritin concentration is normal or increased.

Clinical Presentation of Anemia

Acute-onset anemia presents with cardiorespiratory symptoms, including palpitations, angina, orthostatic light-headedness, and breathlessness.
Chronic anemia presents with weakness, fatigue, headache, orthopnea, dyspnea on exertion, vertigo, faintness, cold sensitivity, and pallor.
IDA is characterized by glossal pain, smooth tongue, reduced salivary flow, pica, and pagophagia.
Vitamin B12 deficiency can cause neurologic effects, such as numbness and paraesthesias, which may precede hematologic changes.
Vitamin B12 deficiency can also cause psychiatric findings, including irritability, depression, and memory impairment.
Anemia with folate deficiency is not associated with neurologic symptoms.

Diagnosis of Anemia

Rapid diagnosis is essential because anemia is often a sign of underlying pathology.
The severity of symptoms does not always correlate with the degree of anemia.
Initial evaluation of anemia involves a complete blood cell count (CBC), reticulocyte index, and examination of the stool for occult blood.
The earliest and most sensitive laboratory change for IDA is decreased serum ferritin (storage iron).

Macrocitic Anemias

Mean corpuscular volume is usually elevated in macrocytic anemias
Vitamin B12 and folate concentrations can be measured to differentiate between the two deficiency anemias