Obstructive And Restrictive Lung Disease

SARCOIDOSIS
A. Systemic disease characterized by noncaseating granulomas in multiple organs;
classically seen in African American females
B. Etiology is unknown; likely due to CD4 • helper T-cell response to an unknown antigen
C. Granulomas most commonly involve the hilar lymph nodes and lung (Fig. 9.15A),
leading to restrictive lung disease.
l. Characteristic stellate inclusions ('asteroid bodies') are often seen within giant
cells of the granulomas .
D. Other commonly involved tissues include the uvea (uveitis), skin (cutaneous
nodules or erythema nodosum), and salivary and lacrimal glands (mimics Sjogren
syndrome); almost any t issue can be involved.
E. Clinical features
l. Dyspnea or cough (most common presenting symptom)
2. Elevated serum ACE
3. Hypercalcemia (1-alpha hydroxylase activity of epithelioid histiocytes converts
vitamin D to its active form)
4. Treatment is steroids; often resolves spontaneously without treatment.

The patient's symptoms of dyspnea and hyper-resonance to percussion suggest the presence of emphysema, a condition characterized by destruction of lung tissue. Decreased serum alpha-1-antitrypsin is the most likely laboratory finding in this case because alpha-1-antitrypsin is a protein that helps protect the lungs from damage caused by enzymes released during inflammation. Deficiency of alpha-1-antitrypsin can lead to the development of emphysema at an early age. The other options are not associated with emphysema.

The ferruginous bodies shown in the figure are long, thin crystals of asbestos that have become encrusted with iron and calcium. The inflammatory reaction incited by these crystals promotes fibrogenesis and resultant pneumoconiosis.
___________________________________________________
Obstructive disease -”COPD” = difficulty with expiratory deflation of the lungs due to anatomic narrowing of airways or reduced elastic recoil


Restrictive disease = difficulty with inspiratory expansion of the lungs due to reduced total lung capacity---eg. chest wall disorders or interstitial or infiltrative lung diseases(acute or chronic) eg pneumoconiosis. Fibrosis often a factor

Bronchiectasis:
= Infection + permanent dilatation of bronchi. Causes: infections and bronchial obstruction (FB, mucus plugs, tumors, intralobar sequestrations, cystic fibrosis, immotile cilia (Kartagener’s synd.)
Infection destroys the elastic tissue in the wall of bronchi; and persistent obstruction --> collapse & fibrosis of alveoli --> increased negativity of the intrathoracic pressure ---> dilatation of weakened bronchi (cylindrical, fusiform or saccular).
Clinically: chronic cough, productive of purulent sputum; may progress to obstructive respiratory insufficiency & cor-pulmonale.

The patient's history of chronic cough, smoking, and physical examination findings of thin cyanotic man with tachypnea and tachycardia suggest a diagnosis of chronic obstructive pulmonary disease (COPD). Increased Reid Index, hypertrophy of mucus glands, and squamous metaplasia are characteristic histological findings seen in COPD. The Reid Index is the ratio of the thickness of the submucosal gland layer to the thickness of the bronchial wall, and an increased Reid Index indicates hypertrophy of mucus glands. Squamous metaplasia is a common histological finding in COPD due to chronic irritation and inflammation of the airways.

The correct answer is dilation of the respiratory bronchioles and alveolar ducts and sacs. This is because the patient's history of smoking and the presence of barrel chest, small heart, and overinflated lungs on chest x-ray suggest the development of chronic obstructive pulmonary disease (COPD). In COPD, the airways become narrowed and the alveoli become overinflated, leading to the dilation of respiratory bronchioles and alveolar ducts and sacs. This can result in severe dyspnea and respiratory failure, as seen in this patient.

EMPHYSEMA
A. Destruction of alveolar air sacs ******************
1. Loss of elastic recoil and collapse of airways during exhalation results in obstruction and air trapping.
B. Due to imbalance of proteases and antiproteases
1. Inflammation in the lung normally leads to release of proteases by neutrophils
and macrophages.
2. a1-antitrypsin (AlAT) neutralizes proteases.
3. Excessive inflammation or lack of AlAT leads to destruction of the alveolar air sacs.

C. Smoking is the most common cause of emphysema.
1. Pollutants in smoke lead to excessive inflammation and protease-mediated damage.
2. Results in centriacinar emphysema that is most severe in the upper lobes

E. Clinical features of emphysema include
1. Dyspnea and cough with mini mal sputum*****************
2. Prolonged expiration with pursed lips ('pink-puffer')
3. Weight loss***********************
4. Increased anterior-posterior diameter of chest ('barrel-chest) ****************
5. Hypoxemia (due to destruction of capillaries in the alveolar sac) and cor pulmonale are late complications.

Omalizumab (Xolair®)

•Chemistry
o IgG monoclonal antibody
• Pharmacokinetics
o Parenteral administration **************
Administration of large doses should be divided over more than one injection site
o Slow absorption
o Bioavailability ~62%
o Undergoes hepatic metabolism, and degradation via the reticuloendothelial system and endothelial cells
o t1/2 ~26 days
o Elimination is primarily through hepatic degradation and bile secretion of intact antibody
• Pharmacodynamics
o Mechanism of Action

Binds IgE antibodies and inhibits their binding to the high-affinity IgE receptor on mast cells and basophils

o Pharmacological Actions/Effects
Inhibits IgE-mediated effects ********
• Inhibits release of early and late phase allergic response mediators
• DECREASES serum IgE levels and expression of high-affinity IgE receptors *******

•Clinical Pharmacology
o Clinical Uses
Therapy of moderate-to-severe, persistent allergic asthma not adequately controlled with ICS
• Lessens asthma severity and reduces corticosteroid requirement
• Reduces the frequency and severity of asthma exacerbations
• Not used to control acute asthmatic attacks
Improvement of symptoms of perennial and seasonal allergic rhinitis
o ADVERSE EFFECTS/TOXICITY
Serious reactions
• Hypersensitivity reactions/anaphylaxis can occur within 2-24 hrs following administration, and > 1 year after initiation of regular treatment (very rare)
• Malignancy, severe thrombocytopenia, severe injection site reactions
Common reactions
• Injection site reaction, viral infection, URI, sinusitis, headache, pharyngitis, helminth infection, arthralgia, pain, fatigue, dizziness, pruritus, dermatitis, earache, fractures
Carries a Black Box Warning regarding ANAPHYLAXIS RISK
o Contraindications
Acute bronchospasm, status asthmaticus, parasitic infections (infection risk may be increased)
Pregnancy/Lactation—Category B/precaution (safety unknown)

Polarized microscopy would be confirmatory in this case because it is used to identify and evaluate lung changes, such as fibrosis and inflammation, which can be seen in individuals with a history of occupational exposure, such as construction workers. It allows for the visualization of tissue structures and can help identify specific patterns associated with certain lung diseases. The other options, Congo red stain, Serum ACE level, and Ziehl-Neelsen stain, are not specific to evaluating lung changes and would not provide confirmatory evidence in this case.

The given answer is the most likely set of clinicolaboratory data that would be found in this case because it is consistent with the patient's history of smoking and the findings of severe atherosclerosis and lung changes. The "pink puffer" appearance, tachypnea, and reduced FEV1/FVC are indicative of chronic obstructive pulmonary disease (COPD), which is commonly seen in smokers. The presence of normoxia (normal oxygen levels) and normocapnia (normal carbon dioxide levels) suggests that the patient's respiratory function is still relatively preserved despite the lung changes. This combination of symptoms and laboratory findings is consistent with a "pink puffer" phenotype of COPD.

Panacinar (or panlobular) emphysema: The entire respiratory acinus, from respiratory bronchiole to alveoli, has expanded. Occurs more commonly in the lower lobes (especially basal segments) and in the anterior margins of the lungs.

Centriacinar (or centrilobular) emphysema: The respiratory bronchiole (proximal and central part of the acinus) has expanded. The distal acinus or alveoli are unchanged. Occurs more commonly in the upper lobes