LUNG DISORDERS

ASTHMA
A chronic inflammatory disorder of the airways that causes recurrent
episodes of wheezing, breathlessness, chest tightness, and cough,
particularly at night and/or early in the morning.

The hallmarks of asthma are intermittent, reversible airway obstruction,

chronic bronchial inflammation with eosinophils, bronchial smooth
muscle cell hypertrophy and hyperreactivity, and increased mucus
secretion.

ETIOLOGY
Asthma tends to “run” in families, but the role of genetics in asthma is
complex. Genome-wide association studies have identified a number of
genetic variants associated with asthma risk, some in genes enocding
factors like the IL-4 receptor that are clearly involved in asthma
pathogenesis.
 However, the precise contribution of asthma-associated genetic variants to the
development of disease remains to be determined.

EPIDEMIOLOGY
Worldwide, it is estimated that approximately 334 million people currently
suffer from asthma, and 250,000 deaths are attributed to the disease each
year. The prevalence of the disease is continuing to grow, and the overall
prevalence is estimated to increase by 100 million by 2025.
PATHOPHYSIOLOGY
Major factors contributing to the development of asthma include genetic
predisposition to type I hypersensitivity, acute and chronic airway
inflammation, and bronchial hyperresponsiveness to a variety of stimuli.

Asthma may be subclassified as atopic or nonatopic. In both types,

episodes of bronchospasm may be triggered by diverse exposures, such
as respiratory infections, airborne irritants, cold air, stress, and exercise.

There also are varying patterns of inflammation eosinophilic, neutrophilic,

mixed inflammatory, and pauci-granulocytic that are associated with
differing etiologies, immunopathologies, and responses to treatment
Airflow limitation in asthma is recurrent and caused by a variety of changes in the airway.

• The early-phase reaction is dominated by bronchoconstriction,

increased mucus production, and vasodilation. Bronchoconstriction is
triggered by mediatorsreleased from mast cells, including histamine,
prostaglandin D2, and leukotrienes LTC4, D4, and E4, and also by reflex
neural pathways.

• The late-phase reaction is inflammatory in nature. Inflammatory

mediators stimulate epithelial cells to produce chemokines that promote
the recruitment of TH2 cells, eosinophils, and other leukocytes, thus
amplifying an inflammatory reaction that is initiated by resident immune
cells.

• Repeated bouts of inflammation lead to structural changes in the

bronchial wall that are collectively referred to as airway remodeling.
These changes include hypertrophy of bronchial smooth muscle and
mucus glands and increased vascularity and deposition of subepithelial
collagen, which may occur as early as several years before initiation of
symptoms.
CLINICAL FEATURES
An attack of asthma is characterized by severe dyspnea and wheezing due
to bronchoconstriction and mucus plugging, which leads to trapping of air in
distal airspaces and progressive hyperinflation of the lungs.
Intervals between attacks are characteristically free from overt respiratory
difficulties, but persistent, subtle deficits can be detected by pulmonary
function tests.
Occasionally a severe paroxysm occurs that does not respond to therapy
and persists for days and even weeks.
Standard therapies include anti-inflammatory drugs, particularly
glucocorticoids, and bronchodilators such as beta-adrenergic drugs and
leukotriene inhibitors.
Another approach called bronchial thermoplasty, which involves controlled
delivery of thermal energy during bronchoscopy to reduce the mass of
smooth muscle and airway responsiveness, is being evaluated in patients
with severe, poorly controlled asthma.
SARCOIDOSIS
A multisystem disease of unknown etiology characterized by noncaseating
granulomatous inflammation in many tissues and organs

ETIOLOGY
Several immunologic abnormalities in sarcoidosis suggest the development of
a cell-mediated response to an unidentified antigen. The process is driven by
CD4+ helper T cells. These immunologic “clues” include the following:
• Intraalveolar and interstitial accumulation of CD4+ TH1 cells,
with peripheral T cell cytopenia.
• Oligoclonal expansion of CD4+ TH1 T cells within the lung as
determined by analysis of T cell receptor rearrangements.
• Increases in TH1 cytokines such as IL-2 and IFN-γ, resulting
in T cell proliferation and macrophage activation.
• Increases in several cytokines in the local environment that
favor recruitment of additional T cells and monocytes and
contribute to the formation of granulomas.
 • Anergy to common skin test antigens such as Candida or purified protein
derivative.
• Polyclonal hypergammaglobulinemia.
• Familial and racial clustering of cases, suggesting the involvement of
genetic factors.

EPIDEMIOLOGY
• A consistent predilection for adults younger than 40 years of age.
• A high incidence in Danish and Swedish populations, and in the United
States among African Americans .
• A higher prevalence among nonsmokers, an association that is virtually
unique to sarcoidosis among pulmonary diseases.
CLINICAL MANIFESTATION
• Lymph node enlargement.
• Eye involvement (sicca syndrome, iritis, or iridocyclitis),
• Skin lesions
• Visceral involvement (liver, skin, bone marrow).
• Lung involvement occurs in 90% of cases, with formation of
granulomas and interstitial fibrosis
TUBERCULOSIS
A communicable chronic granulomatous disease caused by Mycobacterium
tuberculosis. It usually involves the lungs but may affect any organ or tissue
in the body.

EPITIOLOGY
Mycobacterium tuberculosis hominis is responsible for most cases of
tuberculosis. the reservoir of infection typically is found in individuals with active
pulmonary disease. Transmission usually is direct, by inhalation of airborne
organisms in aerosols generated by expectoration or by exposure to
contaminated secretions of infected individuals

Other mycobacteria, particularly Mycobacterium avium complex, are much less

virulent than M. tuberculosis and rarely cause disease in immunocompetent
individuals. However, they cause disease in 10% to 30% of patients with AIDS.
EPIDEMIOLOGY
The World Health Organization (WHO) considers tuberculosis to be the most
common cause of death resulting from a single infectious agent.

It is estimated that 1.7 billion individuals are infected worldwide, with

8 to 10 million new cases and 1.5 million deaths per year.

In the Western world, deaths from tuberculosis peaked in 1800 and steadily
declined throughout the 1800s and 1900s. However, in 1984 the decline in
new cases stopped abruptly, a change that resulted from the increased
incidence of tuberculosis in HIV-infected individuals.

In 2014, there were approximately 9400 new cases of active

tuberculosis in the United States, with nearly 60% of these occurring in
immigrants from countries where tuberculosis is endemic.
PATHOPHYSIOLOGY
Unchecked bacterial growth may lead to haematogenous spread of
bacilli to produce disseminated TB. Disseminated disease with
lesions resembling millet seeds is termed miliary TB. Bacilli can also
spread by erosion of the caseating lesions into the lung airways and
the host becomes infectious to others.

CLINICAL MANIFESTATION
• Coughing for three or more weeks.
• Coughing up blood or mucus.
• Chest pain, or pain with breathing or coughing.
• Unintentional weight loss.
Reference:
Kumar, V., Abbas, A., Aster, J., Robbins Basic Pathology 10th
Edition (2018), W. B. Saunders