Respiratory System – COPD, asthma, Emphysema, Bronchiectasis, Cancer

Disorders of the Upper Respiratory System

a. Acute rhinitis 

  • Common cold: This is the most common of all illnesses and is caused by viruses, especially the adenoviruses. It is manifest by coryza (“runny nose”), sneezing, nasal congestion, and mild sore throat.
  • Allergic rhinitis: This is mediated by an IgE type I immune reaction involving mucosal and
  • submucosal mast cells. It is characterized by increased eosinophils in peripheral blood
  • and nasal discharge.
  • Bacterial infection: This infection may be superimposed on acute viral or allergic rhinitis by injury to mucosal cilia, which may also occur from other environmental factors.
    • Most commonly, the cause is streptococci, staphylococci, or Haemophilus influenzae.
    • Fibrous scarring, decreased vascularity, and atrophy of the epithelium and mucous glands may result.

b. Sinusitis

Sinusitis is inflammation of the paranasal sinuses often caused by extension of nasal cavity or dental infection. It results in obstructed drainage outlets from the sinuses, leading to an accumulation of mucoid secretions or exudate.

c. Laryngitis

Laryngitis is acute inflammation of the larynx produced by viruses or bacteria, irritants, or overuse of the voice. It is characterized by inflammation and edema of the vocal cords, with resultant hoarseness.

d. Acute epiglottitis 

Acute epiglottitis is inflammation of the epiglottis and may be life-threatening in young children. It is usually caused by H. influenzae.

e. Acute laryngo-tracheobronchitis

Acute laryngotracheobronchitis (croup) is acute inflammation of the larynx, trachea, and epiglottis that is potentially life-threatening in infants. It is most often caused by viral infection. Characteristics include a harsh cough and inspiratory stridor.

 

Tumors of the Upper Respiratory System

a. Tumors of the nose and nasal sinuses

  • Angiofibroma is a rare vascular neoplasm most common in the posteriolateral nasal wall of adolescent males. It is histologically benign but locally aggressive.
  • Nasopharyngeal carcinoma (previously known as “lymphoepithelioma”) is most common in Southeast Asia and East Africa and is caused by Epstein-Barr virus.
  • Squamous cell carcinoma is the most frequently occurring malignant nasal tumor.
  • Adenocarcinoma accounts for 5% of malignant tumors of the nose and throat, includes intestinal-type and non-intestinal-type cases.
  • Olfactory neuroblastomas are comprised of small round blue cells set in a neurofibrillary matrix. They arise from the olfactory mucosa and usually in older male patients (unlike pediatric neuroblastoma, which most often occurs in the adrenals/abdomen of infants and young children) .
  • Plasmacytoma is a plasma cell neoplasm that, in its extraosseous form, produces tumors in the upper respiratory System.
  • Embryonal rhabdomyosarcoma is an aggressive mesenchymal malignancy most common in young children.

b. Tumors of the oropharynx

Squamous cell carcinomas account for the vast majority of malignancies in this location and are associated with high-risk human papillomavirus (HPV) (most commonly type 16) ˜80% of cases.

  • Originate mainly in the palantine and lingual tonsils and are nonkeratinizing squamous cell carcinomas with basaloid morphology.
  • When compared to HPV-negative squamous cell tumors from this site, HPV-positive cancers more often present in young, nonsmoking patients and are more likely to have cervical lymph nodal metastases. However, despite higher stage at presentation, their overall prognosis is better.
  • HPV-negative cases are usually associated with tobacco and/or alcohol abuse.

c. Tumors of the larynx

1. Singer’s nodule:

This small, benign laryngeal polyp, usually induced by chronic irritation, such as excessive use of the voice, is associated most commonly with heavy cigarette smoking. It is usually localized to the true vocal cords.

2. Squamous papilloma

  • These are benign neoplasms that are usually centered around the true vocal cords and may rarely undergo malignant change.
  • They are usually attributable to low-risk HPV infections (principally types 6 and 11, the same types responsible for most genital condylomas).
  • In children and adolescents multiple lesions can be seen, sometimes with airwaythreatening extension into the trachea and bronchi (juvenile laryngeal papillomatosis). Recurrence after resection is common.

3. Squamous cell carcinoma

  • This neoplasm is the most common malignant tumor of the larynx and is usually seen in men older than 40 years of age; it is often associated with the combination of cigarette smoking and alcoholism. It is usually not associated with HPV infection in this location.
  • Initially, it most often presents with persistent hoarseness.
  • Glottic carcinoma arises from the true vocal cords. It is the most common laryngeal carcinoma and has the best prognosis.
  • Supraglottic and subglottic carcinomas are less common and typically have a poorer prognosis.

 

Chronic Obstructive Pulmonary Disease (COPD) – (Disorders of Respiratory System) 

COPD is a group of disorders characterized by airflow obstruction. Characteristics include a marked decrease in the 1-second forced expiratory volume (FEV1) and an increased or normal forced vital capacity (FVC), resulting in a decreased FEV1:FVC ratio. COPD is often contrasted with restrictive pulmonary disease, a group of disorders characterized by reduced lung capacity due to either chest wall or skeletal abnormalities, such as kyphoscoliosis, or to interstitial or infiltrative parenchymal disease. In restrictive lung disease, the FEV1 and FVC are both decreased proportionately, resulting in a normal FEV1:FVC ratio.

a. Bronchial asthma (Disorders of Respiratory System) 

Types include extrinsic and intrinsic asthma.

  • Extrinsic (immune) asthma is mediated by a type I hypersensitivity response involving IgE bound to mast cells. Disease begins in childhood, usually in patients with a family history of allergy.
  • Intrinsic (nonimmune) asthma includes asthma associated with chronic bronchitis, as well as other asthma variants such as exercise- or cold-induced asthma. It usually begins in adult life and is not associated with a history of allergy.

Characteristics

  • There is marked episodic dyspnea and wheezing expiration caused by narrowing of the airways. Bronchial asthma is related to increased sensitivity of air passages to stimuli.
  • Morphologic manifestations include bronchial smooth muscle hypertrophy, hyperplasia of goblet cells, thickening and hyalinization of basement membranes, proliferation of eosinophils, and intrabronchial mucous plugs containing whorl-like accumulations of epithelial cells (Curschmann spirals) and crystalloids of eosinophilderived
  • proteins (Charcot-Leyden crystals).

Complications

Complications include superimposed infection, chronic bronchitis, and pulmonary emphysema. Bronchial asthma may lead to status asthmaticus, a prolonged bout of bronchial asthma that can last for days and that responds poorly to therapy. Death can result.

b. Chronic bronchitis (Disorders of Respiratory System) 

  • The clinical definition is a productive cough that occurs during at least three consecutive months over at least two consecutive years.
  • Chronic bronchitis is clearly linked to cigarette smoking and is also associated with air pollution, infection, and genetic factors. It may lead to cor pulmonale.
  • Typical characteristics include hypersecretion of mucus due to marked hyperplasia of mucus-secreting submucosal glands.

c. Emphysema (Disorders of Respiratory System) 

Emphysema is dilation of air spaces with destruction of alveolar walls and lack of elastic recoil. The disease is strongly associated with cigarette smoking. Clinical characteristics include increased anteroposterior diameter of the chest; increased total vital capacity; and hypoxia, cyanosis, and respiratory acidosis.

Types of emphysema

  • Centrilobular emphysema: Dilation of the respiratory bronchioles is most often localized to the upper part of the pulmonary lobes. It is strongly associated with cigarette smoking.
  • Panacinar emphysema: Dilation of the entire acinus, including the alveoli, alveolar ducts, respiratory bronchioles, and terminal bronchioles, is most often distributed uniformly throughout the lung. It is associated with loss of elasticity and sometimes with genetically determined deficiency of α1-antitrypsin (α1-protease inhibitor).
  • Paraseptal emphysema: Dilation involves mainly the distal part of the acinus, including the alveoli and, to a lesser extent, the alveolar ducts. It tends to localize subjacent to the pleura and interlobar septa. It is associated occasionally with large subpleural bullae, or blebs, which can predispose to pneumothorax.
  • Irregular emphysema: Irregular involvement of the acinus with scarring within the walls of enlarged air spaces is usually a complication of various inflammatory processes.

Complications

  • Emphysema is often complicated by, or coexistent with, chronic bronchitis.
  • Interstitial emphysema, in which air escapes into the interstitial tissues of the chest from a tear in the airways, may occur.
  • Other complications of emphysema may include rupture of a surface bleb with resultant pneumothorax.

Causes

Emphysema may result from action of proteolytic enzymes, such as elastase, on the alveolar wall. Elastase can induce destruction of elastin unless neutralized by the antiproteinase-antielastase activities of α1-antitrypsin.

  • Cigarette smoking atSystems neutrophils and macrophages, which are sources of elastase. It also inactivates α1-antitrypsin.
  • Hereditary α1-antitrypsin deficiency accounts for a small subgroup of cases of panacinar emphysema. It is caused by variants in the pi (proteinase inhibitor) gene, localized to chromosome 14.

d. Bronchiectasis (Disorders of Respiratory System)

This condition is permanent abnormal bronchial dilation caused by chronic infection, with inflammation and necrosis of the bronchial wall. Predisposing factors include bronchial obstruction, most often by tumor.

Other predisposing factors include chronic sinusitis accompanied by postnasal drip. Disease rarely may be a manifestation of Kartagener syndrome (sinusitis, bronchiectasis, and situs inversus, sometimes with hearing loss and male sterility), caused by a defect in the motility of respiratory, auditory, and sperm cilia that is referred to as primary ciliary dyskinesia, an uncommon autosomal recessive syndrome.

In this condition, there is a structural defect in dynein arms. Impaired ciliary activity predisposes to infection in the sinuses and bronchi and disturbs embryogenesis, sometimes resulting in situs inversus. Male infertility is an important manifestation of ciliary dyskinesia. Bronchiectasis most often involves the lower lobes of both lungs. Characteristics include production of copious purulent sputum, hemoptysis, and recurrent pulmonary infection that may lead to lung abscess.

 

Restrictive Pulmonary Disease (Disorders of Respiratory System) 

Restrictive pulmonary disease is a group of disorders characterized by reduced expansion of the lung and reduction in total lung capacity. Examples include abnormalities of the chest wall from bony abnormalities or neuromuscular disease that restrict lung expansion. Also included are the interstitial lung diseases, a heterogeneous group of disorders characterized by interstitial accumulations of cells or noncellular material within the alveolar walls that restrict expansion and often interfere with gaseous exchange.

Prominent examples are acute conditions, such as the adult and neonatal respiratory distress syndromes; pneumoconioses, such as coal workers’ pneumoconiosis, silicosis, and asbestosis; diseases of unknown etiology, such as sarcoidosis and idiopathic pulmonary fibrosis; various other conditions, such as eosinophilic granuloma, hypersensitivity pneumonitis, and chemical- or drug-associated disorders, such as berylliosis or the pulmonary fibrosis associated with bleomycin toxicity; and immune disorders, such as systemic lupus erythematosus, systemic sclerosis (scleroderma), Wegener granulomatosis, and Goodpasture syndrome.

 

 

Pulmonary Vascular Disease (Disorders of Respiratory System) 

a. Pulmonary embolism

  • This is found in more than half of all autopsies.
  • Most often, pulmonary embolism originates from venous thrombosis in the lower extremities or pelvis. Rarely, it can be due to nonthrombotic particulate material, such as fat, amniotic flu
  • Pulmonary embolism occurs in clinical settings marked by venous stasis, including primary venous disease, congestive heart failure, prolonged bed rest or immobilization, and prolonged sitting while traveling. Other predisposing factors include cancer, multiple fractures, and the use of oral contraceptives.
  • These emboli can result in hemorrhagic, or red, infarcts, usually in patients with compromised circulation, but embolism can occur without infarction because of the dual blood supply to the lungs.
  • Clinical consequences may vary and range from asymptomatic disease to sudden death.

b. Pulmonary hypertension

  • Primary pulmonary hypertension is a rare disorder of unknown etiology and poor prognosis that arises in the absence of heart or lung disease. It is most common in young women and, when severe, leads to characteristic plexiform lesions on microscopy.
  • Secondary pulmonary hypertension is more common than the primary form.
  • Most often, the cause is COPD. Other causes may be increased pulmonary blood flow, as in congenital left-to right shunt; increased resistance within the pulmonary circulation, from embolism or vasoconstriction secondary to hypoxia; or increased blood viscosity from polycythemia.
  • This is a cause of right ventricular hypertrophy.

c. Pulmonary edema

It’s an intra-alveolar accumulation of fluid. It may be caused by:

  • Increased hydrostatic pressure, as a result of left ventricular failure or mitral stenosis
  • Increased alveolar capillary permeability, as in inflammatory alveolar reactions, resulting from inhalation of irritant gases, pneumonia, shock, sepsis, pancreatitis, uremia, or drug overdose
  • Miscellaneous mechanisms, such as rapid ascent to high altitude

 

Cancers of the Lung (Disorders of Respiratory System) 

Most lung tumors are malignant; those that arise from metastases from primary tumors elsewhere occur more frequently than those that originate in the lung. Primary lung carcinomas were once called “bronchogenic carcinomas,” but this term is now avoided because it is now known that a significant minority has no evidence of bronchial origin.

Lung carcinoma

Lung carcinoma is the leading cause of death from cancer in both men and women. It is increasing in incidence, especially in women, in parallel with cigarette smoking. The majority (85% to 90%) of lung cancers arises in smokers, and the most common tumors in smokers are small cell and squamous cell carcinomas. The incidence of these tumors is directly proportional in incidence to the number of cigarettes smoked daily and to the number of years of smoking. In contrast, lung cancers in never-smokers are most likely to be adenocarcinomas.

Other etio-pathogenic factors:

  • Air pollution
  • Radiation; incidence increased in radium and uranium workers
  • Asbestos; increased incidence with asbestos and greater increase with combination of asbestos and cigarette smoking
  • Industrial exposure to nickel and chromates
  • Genetic; epidermal growth factor receptor gene (EGFR) mutations often identified in nonsmall cell carcinomas (chiefly adenocarcinomas) in never-smokers

Clinical manifestations may include cough, hemoptysis, and bronchial obstruction, often with atelectasis and pneumonitis. The tumor often spreads by local extension into the pleura, pericardium, and/or ribs. Other clinical features include:

  • Superior vena cava syndrome; compression or invasion of the superior vena cava,
  • resulting in facial swelling and cyanosis along with dilation of the veins of the head, neck, and upper extremities
  • Pancoast tumor (superior sulcus tumor); involvement of the apex of the lung, often with Horner syndrome (ptosis, miosis, and anhidrosis), due to involvement of the cervical sympathetic plexus
  • Hoarseness from recurrent laryngeal nerve paralysis
  • Pleural effusion, often bloody; bloody pleural effusion suggests malignancy, tuberculosis, or trauma.
  • Paraneoplastic endocrine syndromes, the most frequent of which is adrenocorticotropic hormone (ACTH) or ACTH-like activity with small cell carcinoma; also of note is the syndrome of inappropriate antidiuretic hormone secretion (SIADH) with small cell carcinoma of the lung and parathyroid-like activity with squamous cell carcinoma.

Classification

For therapeutic purposes, lung carcinomas are often subclassified into small cell carcinoma, which is not considered amenable to surgery, and nonsmall cell carcinoma, in which surgical intervention may be considered. Lung carcinoma is subclassified as
follows:

  1. Squamous cell carcinomas most often arise centrally, range from well to poorly differentiated, occur almost exclusively in smokers, and may be preceded by squamous dysplasia.
  2. Adenocarcinomas most often arise peripherally and are the most common primary lung cancers in women. Although some cases occur in smokers, they are by far the most common lung cancers in never-smokers. They may be preceded by atypical adenomatous hyperplasia. Histologic variants include acinar, papillary, solid with mucus formation, and bronchioloalveolar. These cancers have been associated with mutations in the EGFR and may be amenable to EGFR tyrosine kinase inhibitors.
  3. Bronchioalveolar carcinomas are adenocarcinomas which grow purely along preexisting alveolar walls (lepidic growth). They have not been associated with smoking.
  4. Small cell carcinomas (formerly known as “oat cell” carcinomas) (Figure 14-11) most often arise in the perihilar region and are frequently metastatic at diagnosis. They are characterized by high N:C ratio cells with neuroendocrine features, including immunopositivity for synaptophysin and chromogranin.
  5. Large cell carcinomas are poorly differentiated tumors with no evidence of squamous or glandular differentiation which do not meet criteria for small cell carcinoma; this is a diagnosis of exclusion.

Carcinoid tumors

Carcinoid tumors account for 1% to 2% of all primary lung tumors and are thought to arise from normal neuroendocrine components of the bronchial epithelium.

  • Most cases are slow-growing, indolent tumors which do not metastasize and have excellent prognosis with appropriate surgery (5-year survival: 90%). These are known as typical carcinoids.
  • More aggressive behavior has been observed in a subset of cases with increased mitoses, tumor necrosis, and cytologic atypia. These have historically been deemed atypical carcinoids, although current thinking suggests that these ought to be reclassified alongside small cell carcinoma as part of the spectrum of neuroendocrine carcinoma.