5. Bronchial Obstruction

Broncho-obstructive Broncho-obstructive syndromesyndrome

Broncho-obstructive Broncho-obstructive syndromesyndrome

Broncho-obstructive syndromeBroncho-obstructive syndrome is the is the collective term including a symptom-collective term including a symptom-complex of specificly outlined clinical complex of specificly outlined clinical implications of disturbance of bronchial implications of disturbance of bronchial passableness, having in the basis passableness, having in the basis narrowing or an occlusion of respiratory narrowing or an occlusion of respiratory tracts.tracts.

Occurrence and its development are Occurrence and its development are influenced by various factors and, first of influenced by various factors and, first of all, a respiratory virus infection all, a respiratory virus infection contamination contamination

Anatomy of the Anatomy of the Lower Respiratory SystemLower Respiratory System

Trachea

LeftRight

Main bronchi

Bronchus

Bronchioles

Acinus

Alveolus

Acinus

Alveolus

Capillaries

rigid because ofC-shapedcartilage rings

Capillary

Alveolarspace

Attenuatedepithelium

Anatomy of the AirwaysAnatomy of the Airways

Trachea and major bronchi Bronchioles

MucusCiliaSecretory cells

Ciliated cells

Basal membrane

Submucosa

Smooth muscle

Connective tissue

Cartilage

Mucous membrane

Epithelium

Airway mucous membrane

Causes of Bronchial Causes of Bronchial obstruction obstruction

• Pulmonary secretions Pulmonary secretions • Foreign body Foreign body • Bronchogenic carcinoma • Aspiration Aspiration • Extrinsic compression by a Extrinsic compression by a

mass mass • Metastatic tumour • Asthma • COPD • Emphysema • Bronchiectasis • Fibrosing alveolitis • Lung collapse Lung collapse

• Lung fibrosis • Tracheomalacia Tracheomalacia • Tracheal stenosis • Bronchial stenosis • Endobronchial tumors Endobronchial tumors • Enlarged lymph nodes • Tuberculosis • Histoplasmosis • Enlarged pulmonary Enlarged pulmonary

arteries arteries • Enlarged atrium from any Enlarged atrium from any

causes causes • Bronchial oedema Bronchial oedema • Asthma • COPD

BRONCHITISBRONCHITIS Bronchitis is characterized by Bronchitis is characterized by

inflammation of the bronchial tubes (or inflammation of the bronchial tubes (or bronchi), which are the air passages that bronchi), which are the air passages that extend from the trachea into the small extend from the trachea into the small airways and and alveoliairways and and alveoli..

ETIOLOGYETIOLOGY

ViralViral – – influenza A+B, parainfluenza, influenza A+B, parainfluenza, rinoviruses, Coxsackie, rinoviruses, Coxsackie, enteroviruses, mixovirusesenteroviruses, mixoviruses

ETIOLOGY (con---d)ETIOLOGY (con---d)

BacterialBacterial – Pneumococcus, – Pneumococcus, streptococcus, Haemofiulus streptococcus, Haemofiulus influenzae, Moraxella catarralis. influenzae, Moraxella catarralis. Mycoplasma pneumoniae and Mycoplasma pneumoniae and clamydii also can be causative agent clamydii also can be causative agent in 10-20% of all acute bronchitis, in 10-20% of all acute bronchitis, predominantly at young persons.predominantly at young persons.

Chemical Chemical – aerosols, smoke, dusts.– aerosols, smoke, dusts.

CLASSIFICATIONCLASSIFICATION

– Catarrhal Catarrhal – UlcerativeUlcerative– HemorrhagicHemorrhagic– PseudomembranousPseudomembranous– Capillary Capillary

CLASSIFICATIONCLASSIFICATION

AcuteAcute ((Acute bronchitis is Acute bronchitis is manifested by cough and, manifested by cough and, occasionally, sputum production that occasionally, sputum production that last for no more than 3 weekslast for no more than 3 weeks))

ChronicChronic ((Chronic bronchitis is Chronic bronchitis is defined clinically as cough with defined clinically as cough with sputum expectoration for at least sputum expectoration for at least 3 3 months months during a period of during a period of 2 2 consecutive yearsconsecutive years))

PATHOGENESISPATHOGENESIS

Respiratory viruses are the most Respiratory viruses are the most common causes of acute bronchitis. common causes of acute bronchitis. The most common viruses include The most common viruses include influenza A and B, parainfluenza, influenza A and B, parainfluenza, respiratory syncytial virus, and respiratory syncytial virus, and coronavirus, although an etiologic coronavirus, although an etiologic agent is identified only in a minority agent is identified only in a minority of cases of cases

PATHOGENESIS (con---d)PATHOGENESIS (con---d)

During an episode of acute bronchitis, the cells of During an episode of acute bronchitis, the cells of the bronchial-lining tissue are irritated and the the bronchial-lining tissue are irritated and the mucous membrane becomes hyperemic and mucous membrane becomes hyperemic and edematous, diminishing bronchial mucociliary edematous, diminishing bronchial mucociliary function. Consequently, the air passages become function. Consequently, the air passages become clogged by debris and irritation increases. In clogged by debris and irritation increases. In response, copious secretion of mucus develops, response, copious secretion of mucus develops, which causes the characteristic cough of bronchitis. which causes the characteristic cough of bronchitis. For instance, with mycoplasmal pneumonia, For instance, with mycoplasmal pneumonia, bronchial irritation results from the attachment of bronchial irritation results from the attachment of the organism (the organism (Mycoplasma pneumoniaeMycoplasma pneumoniae) to the ) to the respiratory mucosa, with eventual sloughing of respiratory mucosa, with eventual sloughing of affected cells. affected cells.

PATHOGENESIS (con---d)PATHOGENESIS (con---d)

Acute bronchitis usually lasts Acute bronchitis usually lasts approximately 10 days. If the approximately 10 days. If the inflammation extends downward to inflammation extends downward to the ends of the bronchial tree, into the ends of the bronchial tree, into the small bronchi (bronchioles), and the small bronchi (bronchioles), and then into the air sacs, then into the air sacs, bronchopneumonia results bronchopneumonia results

COMPLAINSCOMPLAINS

Cough Cough – initially dry and later - – initially dry and later - productive (may be purulent) in productive (may be purulent) in evolution of the disease.evolution of the disease.

COMPLAINSCOMPLAINS Cough and sputum production: Cough is the most Cough and sputum production: Cough is the most

commonly observed symptom. It begins early in the commonly observed symptom. It begins early in the course of many acute respiratory tract infections and course of many acute respiratory tract infections and becomes more prominent as the disease progresses. becomes more prominent as the disease progresses. Acute bronchitis may be indistinguishable from an upper Acute bronchitis may be indistinguishable from an upper respiratory tract infection during the first few days; respiratory tract infection during the first few days; however, cough lasting greater than 5 days may suggest however, cough lasting greater than 5 days may suggest acute bronchitis.3 In patients with acute bronchitis, acute bronchitis.3 In patients with acute bronchitis, cough generally lasts from 10-20 days. Sputum cough generally lasts from 10-20 days. Sputum production is reported in approximately half the patients production is reported in approximately half the patients in whom cough occurred. Sputum may be clear, yellow, in whom cough occurred. Sputum may be clear, yellow, green, or even blood-tinged. Purulent sputum is reported green, or even blood-tinged. Purulent sputum is reported in 50% of persons with acute bronchitis. Changes in in 50% of persons with acute bronchitis. Changes in sputum color are due to peroxidase released by sputum color are due to peroxidase released by leukocytes in sputum; therefore, color alone cannot be leukocytes in sputum; therefore, color alone cannot be considered indicative of bacterial infe considered indicative of bacterial infe

ComplainsComplains

Dyspnea Dyspnea – due to obstruction of – due to obstruction of bronchial airways or inflammation of bronchial airways or inflammation of upper respiratory tract.upper respiratory tract.

Dyspnea and cyanosis: These are not Dyspnea and cyanosis: These are not observed in adults unless the patient observed in adults unless the patient has underlying COPD or another has underlying COPD or another condition that impairs lung functioncondition that impairs lung function..

ComplainsComplains

Raw or burning dull Raw or burning dull pain substernally pain substernally exacerbated by deep breathing and exacerbated by deep breathing and coughingcoughing

Headache, weakness, subfebrile Headache, weakness, subfebrile temperature.temperature.

Sore throat Sore throat Runny or stuffy nose Runny or stuffy nose

ComplainsComplains Muscle aches Muscle aches Extreme fatigue Extreme fatigue Fever: This is a relatively unusual sign Fever: This is a relatively unusual sign

and, when accompanied by cough, and, when accompanied by cough, suggests either influenza or pneumonia. suggests either influenza or pneumonia.

Nausea, vomiting, and diarrhea: These Nausea, vomiting, and diarrhea: These are rare. Severe cases may cause general are rare. Severe cases may cause general malaise and chest pain. With severe malaise and chest pain. With severe tracheal involvement, burning, substernal tracheal involvement, burning, substernal chest pain associated with respiration, chest pain associated with respiration, and coughing may occur. and coughing may occur.

Clinical examinationClinical examination

The physical examination findings in The physical examination findings in acute bronchitis can vary from acute bronchitis can vary from normal-to-pharyngeal erythema, normal-to-pharyngeal erythema, localized lymphadenopathy, and localized lymphadenopathy, and rhinorrhea to coarse rhonchi and rhinorrhea to coarse rhonchi and wheezes that change in location and wheezes that change in location and intensity after a deep and productive intensity after a deep and productive cough cough

CLINICAL EXAMINATIONCLINICAL EXAMINATION

Hiperemia of the skin if fever is presentHiperemia of the skin if fever is present Vocal fremitus and percussion sound Vocal fremitus and percussion sound

unchangedunchanged Auscultation – sharp vesicular breathing, Auscultation – sharp vesicular breathing,

ronflant crackles if pathologic process is ronflant crackles if pathologic process is in the big and medium bronchis and in the big and medium bronchis and sibilant crackles if pathological process sibilant crackles if pathological process is in the small bronchis. This crackles is in the small bronchis. This crackles are changed after the coughing.are changed after the coughing.

CLINICAL EXAMINATION (con---CLINICAL EXAMINATION (con---d)d)

In acute brocnchiolitis (in lesion of small airways due In acute brocnchiolitis (in lesion of small airways due to viral infection) clinical findings will present:to viral infection) clinical findings will present:

high fever (>38°C)high fever (>38°C) pronounced dyspneapronounced dyspnea dry cough or with small amount of sputumdry cough or with small amount of sputum pain in the chest due to overload of the muscles in pain in the chest due to overload of the muscles in

the time of coughingthe time of coughing cyanosis is presentcyanosis is present superficial tahypnoesuperficial tahypnoe participation of auxillary muscles in the respirationparticipation of auxillary muscles in the respiration chest fixed in inspirechest fixed in inspire percussion – hyperresonant soundpercussion – hyperresonant sound auscultation – decreased vesicular breathing, auscultation – decreased vesicular breathing,

crepitation cracklescrepitation crackles

CLINICAL EXAMINATION (con---CLINICAL EXAMINATION (con---d)d)

Also note the following:Also note the following:

Sustained heave along the left sternal Sustained heave along the left sternal border indicates right ventricular border indicates right ventricular hypertrophy secondary to chronic hypertrophy secondary to chronic bronchitis. bronchitis.

Clubbing on the digits and peripheral and peripheral cyanosis indicate cystic fibrosis. indicate cystic fibrosis.

Bullous myringitis may suggest Bullous myringitis may suggest mycoplasmal pneumonia. mycoplasmal pneumonia.

Conjunctivitis, adenopathy, and rhinorrhea Conjunctivitis, adenopathy, and rhinorrhea suggest adenovirus infectionsuggest adenovirus infection

LABORATORY FINDINGSLABORATORY FINDINGS

Chest X-ray remains unchangedChest X-ray remains unchanged General blood test – leucocytosis General blood test – leucocytosis

with neutrophilliawith neutrophillia Sputum analysis – leucocytosis, Sputum analysis – leucocytosis,

bacteriabacteria

ComplicationsComplications Complications occur in approximately 10% of Complications occur in approximately 10% of

patients with acute bronchitis and include the patients with acute bronchitis and include the following: following:

Bacterial superinfection Bacterial superinfection Lower respiratory tract infection and pneumonia: Lower respiratory tract infection and pneumonia:

Less than 5% of patients with bronchitis develop Less than 5% of patients with bronchitis develop pneumonia. The incidence of subsequent pneumonia. The incidence of subsequent pneumonia, however, remains unaffected by the pneumonia, however, remains unaffected by the use of antibiotics. use of antibiotics.

Chronic bronchitis: Repeated episodes of acute Chronic bronchitis: Repeated episodes of acute bronchitis may lead to chronic bronchitis. bronchitis may lead to chronic bronchitis.

Reactive airway disease: Acute bronchitis may lead Reactive airway disease: Acute bronchitis may lead to reactive airway disease. to reactive airway disease.

acute bronchiolitisacute bronchiolitis HemoptysisHemoptysis

EVOLUTIONEVOLUTION

Usually 7-10 daysUsually 7-10 days

PrognosisPrognosis

Patients with acute bronchitis have a Patients with acute bronchitis have a good prognosisgood prognosis

Chronic bronchitisChronic bronchitis

Chronic bronchitis Chronic bronchitis is defined is defined clinically as clinically as cough with sputum cough with sputum expectoration for at least expectoration for at least 3 months 3 months during a period of during a period of 2 consecutive 2 consecutive years. years.


Chronic bronchitis is associated with Chronic bronchitis is associated with hypertrophy of the mucus-producing hypertrophy of the mucus-producing glands found in the mucosa of large glands found in the mucosa of large cartilaginous airways.cartilaginous airways.


As the disease advances, progressive As the disease advances, progressive airflow limitation occurs, usually in airflow limitation occurs, usually in association with pathologic changes of association with pathologic changes of emphysema. This condition is called . This condition is called chronic obstructive pulmonary disease (COPD). (COPD).


When a stable patient experiences When a stable patient experiences sudden clinical deterioration with sudden clinical deterioration with increased sputum volume, sputum increased sputum volume, sputum purulence, and/or worsening of purulence, and/or worsening of shortness of breath, this is referred shortness of breath, this is referred to as an acute exacerbation of to as an acute exacerbation of chronic bronchitis as long as chronic bronchitis as long as conditions other than acute conditions other than acute tracheobronchitis are ruled out. tracheobronchitis are ruled out.


Chronic bronchitis is a condition Chronic bronchitis is a condition associated with excessive associated with excessive tracheobronchial mucus production tracheobronchial mucus production sufficient to cause cough with sufficient to cause cough with expectoration for at expectoration for at least 3 least 3 months for more than 2 consecutive months for more than 2 consecutive yearsyears. The alveolar epithelium is both . The alveolar epithelium is both the target and the initiator of the target and the initiator of inflammation in chronic bronchitis. inflammation in chronic bronchitis.


A predominance of neutrophils and the A predominance of neutrophils and the peribronchial distribution of fibrotic changes peribronchial distribution of fibrotic changes result from the action of interleukin 8, result from the action of interleukin 8, colony-stimulating factors, and other colony-stimulating factors, and other chemotactic and proinflammatory chemotactic and proinflammatory cytokines. Airway epithelial cells release cytokines. Airway epithelial cells release these inflammatory mediators in response these inflammatory mediators in response to toxic, infectious, and inflammatory to toxic, infectious, and inflammatory stimuli, in addition to decreased release of stimuli, in addition to decreased release of regulatory products such as ACE or neutral regulatory products such as ACE or neutral endopeptidase. endopeptidase.

BRONCHUS, NORMAL AND BRONCHUS, NORMAL AND CHRONIC BRONCHITISCHRONIC BRONCHITIS

Note the increased thickness of bronchial mucous glands in the Note the increased thickness of bronchial mucous glands in the submucosa of the image with chronic bronchitis (bottom) compared submucosa of the image with chronic bronchitis (bottom) compared

to the normal bronchus (top image).to the normal bronchus (top image).

Chronic bronchitisChronic bronchitis Chronic bronchitis can be Chronic bronchitis can be

categorized ascategorized as:: simplesimple chronic bronchitis, chronic bronchitis, chronic mucopurulent chronic mucopurulent bronchitis, or bronchitis, or

chronic bronchitis with chronic bronchitis with obstruction. obstruction.

Chronic bronchitisChronic bronchitis Mucoid sputum production Mucoid sputum production

characterizes simple chronic characterizes simple chronic bronchitis.bronchitis.

Persistent or recurrent purulent Persistent or recurrent purulent sputum production in the absence of sputum production in the absence of localized suppurative disease, such localized suppurative disease, such as as bronchiectasis, characterizes , characterizes chronic mucopurulent bronchitis. chronic mucopurulent bronchitis.

Chronic bronchitis with obstruction Chronic bronchitis with obstruction must be distinguished from chronic must be distinguished from chronic infective infective asthma..


The differentiation is based mainly on The differentiation is based mainly on the history of the clinical illness. the history of the clinical illness. Patients who have chronic bronchitis Patients who have chronic bronchitis with obstruction present with a long with obstruction present with a long history of productive cough and a late history of productive cough and a late onset of wheezing, whereas patients onset of wheezing, whereas patients who have asthma with chronic who have asthma with chronic obstruction have a long history of obstruction have a long history of wheezing with a late onset of productive wheezing with a late onset of productive cough.cough.


Chronic bronchitis may result from a series of Chronic bronchitis may result from a series of attacks of acute bronchitis, or it may evolve attacks of acute bronchitis, or it may evolve gradually because of heavy smoking or inhalation gradually because of heavy smoking or inhalation of air contaminated with other pollutants in the of air contaminated with other pollutants in the environment. When so-called smoker's cough is environment. When so-called smoker's cough is continual rather than occasional, the mucus-continual rather than occasional, the mucus-producing layer of the bronchial lining has probably producing layer of the bronchial lining has probably thickened, narrowing the airways to the point thickened, narrowing the airways to the point where breathing becomes increasingly difficult. where breathing becomes increasingly difficult. With immobilization of the cilia that sweep the air With immobilization of the cilia that sweep the air clean of foreign irritants, the bronchial passages clean of foreign irritants, the bronchial passages become more vulnerable to further infection and become more vulnerable to further infection and the spread of tissue damage. the spread of tissue damage.


Chronic bronchitisChronic bronchitis A growing body of literature has demonstrated A growing body of literature has demonstrated

that specific occupational exposures are that specific occupational exposures are associated with the symptoms of chronic associated with the symptoms of chronic bronchitis. The list of agents includes coal, bronchitis. The list of agents includes coal, manufactured vitreous fibers, oil mist, cement, manufactured vitreous fibers, oil mist, cement, silica, silicates, osmium, vanadium, welding silica, silicates, osmium, vanadium, welding fumes, organic dusts, engine exhausts, fire fumes, organic dusts, engine exhausts, fire smoke, and secondhand cigarette smoke.smoke, and secondhand cigarette smoke.

The most common risk factors for acute The most common risk factors for acute exacerbations of chronic bronchitis are smoking, exacerbations of chronic bronchitis are smoking, advanced age, and low advanced age, and low forced expiratory forced expiratory volume in one second volume in one second (FEV1) (FEV1)

Chronic bronchitis CXRChronic bronchitis CXR

Chronic bronchitis cannot be Chronic bronchitis cannot be diagnosed radiologically. Although diagnosed radiologically. Although findings such as increased lung findings such as increased lung markings or tubular opacities, markings or tubular opacities, bronchial wall cuffing (thickening) bronchial wall cuffing (thickening) can be seen with bronchitis, they are can be seen with bronchitis, they are nonspecific. nonspecific.

Chronic bronchitis CXRChronic bronchitis CXR

EmphysemaEmphysema

Emphysema is Emphysema is chronic obstructive pulmonary disease (COPD). .

EmphysemaEmphysema

Emphysema is defined pathologically Emphysema is defined pathologically as an abnormal permanent as an abnormal permanent enlargement of air spaces distal to enlargement of air spaces distal to the terminal bronchioles, the terminal bronchioles, accompanied by the destruction of accompanied by the destruction of alveolar walls and without obvious alveolar walls and without obvious fibrosis. fibrosis.

EmphysemaEmphysema

Emphysema frequently occurs in Emphysema frequently occurs in association with association with chronic bronchitischronic bronchitis. . These 2 entities have been These 2 entities have been traditionally grouped under the traditionally grouped under the umbrella term COPD. Patients have umbrella term COPD. Patients have been classified as having COPD with been classified as having COPD with either emphysema or chronic either emphysema or chronic bronchitis predominance. bronchitis predominance.

EmphysemaEmphysema

The current definition of COPD put The current definition of COPD put forth by the Global Initiative for forth by the Global Initiative for Chronic Obstructive Lung Disease Chronic Obstructive Lung Disease (GOLD) does not distinguish between (GOLD) does not distinguish between emphysema and chronic bronchitis emphysema and chronic bronchitis

ClassificationClassification

The 3 described morphological types The 3 described morphological types of emphysema are of emphysema are

centriacinar, centriacinar, panacinar, and panacinar, and paraseptal. paraseptal.

Centriacinar emphysema Centriacinar emphysema begins in the begins in the respiratory bronchioles and spreads respiratory bronchioles and spreads peripherally. Also termed centrilobular peripherally. Also termed centrilobular emphysema, this form is associated with emphysema, this form is associated with long-standing cigarette smoking and long-standing cigarette smoking and predominantly involves the upper half of predominantly involves the upper half of the lungs. the lungs.

Panacinar emphysema Panacinar emphysema destroys the destroys the entire alveolus uniformly and is entire alveolus uniformly and is predominant in the lower half of the predominant in the lower half of the lungs. Panacinar emphysema generally is lungs. Panacinar emphysema generally is observed in patients with observed in patients with homozygous homozygous alpha1-antitrypsin (AAT) alpha1-antitrypsin (AAT) deficiencydeficiency. In people who smoke, focal . In people who smoke, focal panacinar emphysema at the lung bases panacinar emphysema at the lung bases may accompany centriacinar may accompany centriacinar emphysema. emphysema.

Paraseptal emphysema, Paraseptal emphysema, also known as also known as distal acinar emphysema, preferentially distal acinar emphysema, preferentially involves the distal airway structures, involves the distal airway structures, alveolar ducts, and alveolar sacs. The alveolar ducts, and alveolar sacs. The process is localized around the septae of process is localized around the septae of the lungs or pleura. Although airflow the lungs or pleura. Although airflow frequently is preserved, the apical bullae frequently is preserved, the apical bullae may lead to spontaneous pneumothorax. may lead to spontaneous pneumothorax. Giant bullae occasionally cause severe Giant bullae occasionally cause severe compression of adjacent lung tissue. compression of adjacent lung tissue.

Gross pathology of bullous Gross pathology of bullous emphysema shows emphysema shows bullae bullae on the on the

surface of the lungs.surface of the lungs.

CausesCauses

Cigarette smoking: Smoking is by far Cigarette smoking: Smoking is by far the single most clearly established the single most clearly established environmental risk factor for environmental risk factor for emphysema and chronic bronchitis. emphysema and chronic bronchitis. One in 5 persons One in 5 persons who smoke who smoke develops COPD, and 80-90% of COPD develops COPD, and 80-90% of COPD patients have a smoking history. patients have a smoking history.

CausesCauses

AAT AAT ((alpha1-antitrypsinalpha1-antitrypsin) ) deficiency deficiency syndrome: This syndrome leads to syndrome: This syndrome leads to protease-antiprotease imbalance and protease-antiprotease imbalance and unopposed action of neutrophil unopposed action of neutrophil elastases. elastases.

CausesCauses Persons who use intravenous drugs, as follows:Persons who use intravenous drugs, as follows: Emphysema occurs in approximately 2% of persons Emphysema occurs in approximately 2% of persons

who use intravenous drugs and is attributed to who use intravenous drugs and is attributed to pulmonary vascular damage that results from the pulmonary vascular damage that results from the insoluble filler (eg, cornstarch, cotton fibers, insoluble filler (eg, cornstarch, cotton fibers, cellulose, talc) contained in cellulose, talc) contained in methadone or methadone or methylphenidatemethylphenidate..

The bullous cysts found in association with The bullous cysts found in association with intravenous use of intravenous use of cocaine or heroincocaine or heroin occur occur predominantly in the upper lobes. In contrast, predominantly in the upper lobes. In contrast, methadone and methylphenidatemethadone and methylphenidate injections are injections are associated with basilar and panacinar emphysema.associated with basilar and panacinar emphysema.

CausesCauses

IImmune deficiency syndromes, as follows:mmune deficiency syndromes, as follows: Human immunodeficiency virus (HIV) infection Human immunodeficiency virus (HIV) infection

was found to be an independent risk factor for was found to be an independent risk factor for COPD, even after controlling for confounding COPD, even after controlling for confounding variables such as smoking, intravenous drug variables such as smoking, intravenous drug use, race, and age.use, race, and age.77

Apical and cortical bullous lung damage occurs Apical and cortical bullous lung damage occurs in patients who have autoimmune deficiency in patients who have autoimmune deficiency syndrome and syndrome and Pneumocystis cariniiPneumocystis carinii infection. infection. Reversible pneumatoceles are observed in 10-Reversible pneumatoceles are observed in 10-20% of patients with this infection.20% of patients with this infection.

CausesCauses

Vasculitis syndrome, as follows:Vasculitis syndrome, as follows: Hypocomplementemic vasculitis Hypocomplementemic vasculitis

urticaria syndrome (HVUS) may be urticaria syndrome (HVUS) may be associated with obstructive lung associated with obstructive lung disease.disease.

Other symptoms include angioedema, Other symptoms include angioedema, nondeforming arthritis, sinusitis, nondeforming arthritis, sinusitis, conjunctivitis, and pericarditis.conjunctivitis, and pericarditis.

CausesCauses

Connective-tissue disorders, as follows:Connective-tissue disorders, as follows: Cutis laxaCutis laxa is a disorder of elastin that is is a disorder of elastin that is

characterized most prominently by the characterized most prominently by the appearance of premature aging. The appearance of premature aging. The disease usually is congenital, with various disease usually is congenital, with various forms of inheritance (ie, dominant, forms of inheritance (ie, dominant, recessive). Precocious emphysema has recessive). Precocious emphysema has been described in association with cutis been described in association with cutis laxa as early as the neonatal period or laxa as early as the neonatal period or infancy. The pathogenesis of this disorder infancy. The pathogenesis of this disorder includes a defect in the synthesis of includes a defect in the synthesis of elastin or tropoelastin.elastin or tropoelastin.

CausesCauses

Marfan syndromeMarfan syndrome is an autosomal is an autosomal dominant inherited disease of type I dominant inherited disease of type I collagen characterized by abnormal collagen characterized by abnormal length of the extremities, subluxation length of the extremities, subluxation of the lenses, and cardiovascular of the lenses, and cardiovascular abnormality. Pulmonary abnormality. Pulmonary abnormalities, including emphysema, abnormalities, including emphysema, have been described in have been described in approximately 10% of patients.approximately 10% of patients.

CausesCauses

Ehlers-Danlos syndromeEhlers-Danlos syndrome refers to a refers to a group of inherited connective-tissue group of inherited connective-tissue disorders with manifestations that disorders with manifestations that include hyperextensibility of the skin include hyperextensibility of the skin and joints, easy bruisability, and and joints, easy bruisability, and pseudotumors.pseudotumors.

CausesCauses

Salla disease, Salla disease, as follows:as follows: Salla disease is an autosomal recessive storage Salla disease is an autosomal recessive storage

disorder described in Scandinavia; the disease disorder described in Scandinavia; the disease is characterized by intralysosomal accumulation is characterized by intralysosomal accumulation of sialic acid in various tissues.of sialic acid in various tissues.

The most important clinical manifestations are The most important clinical manifestations are severe mental retardation, ataxia, and severe mental retardation, ataxia, and nystagmus.nystagmus.

Precocious emphysema has been described and Precocious emphysema has been described and likely is secondary to impaired inhibitory likely is secondary to impaired inhibitory activity of serum trypsin.activity of serum trypsin.

PathophysiologyPathophysiology

Emphysema is a pathological diagnosis defined Emphysema is a pathological diagnosis defined by permanent enlargement of airspaces distal to by permanent enlargement of airspaces distal to the terminal bronchioles. This leads to a dramatic the terminal bronchioles. This leads to a dramatic decline in the alveolar surface area available for decline in the alveolar surface area available for gas exchange. Furthermore, loss of alveoli leads gas exchange. Furthermore, loss of alveoli leads to airflow limitation by to airflow limitation by 2 mechanisms2 mechanisms::

First, First, loss of the alveolar walls results in a loss of the alveolar walls results in a decrease in elastic recoil, which leads to airflow decrease in elastic recoil, which leads to airflow limitation.limitation.

Second, Second, loss of the alveolar supporting loss of the alveolar supporting structure leads to airway narrowing, which structure leads to airway narrowing, which further limits airflow. further limits airflow.

INFLAMMATION

Small airway diseaseAirway inflammationAirway remodeling

Parenchymal destructionLoss of alveolar attachments

Decrease of elastic recoil

AIRFLOW LIMITATION


Emphysema commonly presents with Emphysema commonly presents with chronic bronchitis. chronic bronchitis. Chronic bronchitis leads to Chronic bronchitis leads to obstruction by causing narrowing of both the obstruction by causing narrowing of both the large and small (<2 mm) airways. In the large large and small (<2 mm) airways. In the large airways, an increase in Goblet cells, squamous airways, an increase in Goblet cells, squamous metaplasia of ciliary epithelial cells, and loss of metaplasia of ciliary epithelial cells, and loss of serous acini can be seen. In the small airways, serous acini can be seen. In the small airways, Goblet cell metaplasia, smooth muscle Goblet cell metaplasia, smooth muscle hyperplasia, and subepithelial fibrosis can be hyperplasia, and subepithelial fibrosis can be seen. In healthy individuals, small airways seen. In healthy individuals, small airways contribute little to airway resistance; however, in contribute little to airway resistance; however, in COPD patients, these become the main site of COPD patients, these become the main site of airflow limitation. airflow limitation.

PathogenesisPathogenesis Most of cases of COPD are the result of exposure to Most of cases of COPD are the result of exposure to

noxious stimuli, most often cigarette smoke. The normal noxious stimuli, most often cigarette smoke. The normal inflammatory response is amplified in persons prone to inflammatory response is amplified in persons prone to COPD development.COPD development. Genetics are believed to play a role Genetics are believed to play a role in this response because not all smokers develop the in this response because not all smokers develop the disease. The cellular composition of airway inflammation disease. The cellular composition of airway inflammation is predominantly mediated by neutrophils, macrophages, is predominantly mediated by neutrophils, macrophages, and lymphocytes. These cells release chemotactic and lymphocytes. These cells release chemotactic factors to recruit more cells (proinflammatory cytokines factors to recruit more cells (proinflammatory cytokines that amplify the inflammation) and growth factors that that amplify the inflammation) and growth factors that promote structural change. promote structural change.

The inflammation is further amplified by oxidative stress The inflammation is further amplified by oxidative stress and protease production. Oxidants are produced from and protease production. Oxidants are produced from cigarette smoke and released from inflammatory cells. cigarette smoke and released from inflammatory cells. Proteases are produced by inflammatory and epithelial Proteases are produced by inflammatory and epithelial cells. This leads to a protease-antiprotease imbalance cells. This leads to a protease-antiprotease imbalance that leads to destruction of elastin and other structural that leads to destruction of elastin and other structural elements. This is believed to be central in the elements. This is believed to be central in the development of emphysema. development of emphysema.

Pathogenesis of COPDPathogenesis of COPD

NOXIOUS AGENT(tobacco smoke, pollutants, occupational agent)

COPD

Genetic factors

Respiratory infection

Other

Alpha1-antitrypsin Alpha1-antitrypsin deficiencydeficiency

AAT is a glycoprotein member of the serine AAT is a glycoprotein member of the serine protease inhibitor family that is synthesized protease inhibitor family that is synthesized in the liver and is secreted into the blood in the liver and is secreted into the blood stream. The main purpose of this 394–amino stream. The main purpose of this 394–amino acid, single-chain protein is to neutralize acid, single-chain protein is to neutralize neutrophil elastase in the lung interstitium neutrophil elastase in the lung interstitium and to protect the lung parenchyma from and to protect the lung parenchyma from elastolytic breakdown. Severe AAT deficiency elastolytic breakdown. Severe AAT deficiency predisposes to unopposed elastolysis with the predisposes to unopposed elastolysis with the clinical sequela of an early onset of panacinar clinical sequela of an early onset of panacinar emphysema. emphysema.

Alpha1-antitrypsin Alpha1-antitrypsin deficiencydeficiency

Deficiency of AAT is inherited as an Deficiency of AAT is inherited as an autosomal codominant condition. The gene autosomal codominant condition. The gene is located on the long arm of chromosome is located on the long arm of chromosome 14 and has been sequenced and cloned. 14 and has been sequenced and cloned. The most common type of severe AAT The most common type of severe AAT deficiency occurs in individuals who are deficiency occurs in individuals who are homozygous for the Z-type protein. homozygous for the Z-type protein. Homozygous individuals (Homozygous individuals (PIZZPIZZ) have serum ) have serum levels well below the reference range levels levels well below the reference range levels (reference range, 20-53 mmol/L). The risk (reference range, 20-53 mmol/L). The risk of emphysema occurs below a threshold of of emphysema occurs below a threshold of 11 mmol/L. 11 mmol/L.

ComplainsComplains Cough:Cough: intermittent or dailyintermittent or daily present throughout day- seldom only nocturnal present throughout day- seldom only nocturnal Sputum:Sputum: Any pattern of chronic sputum productionAny pattern of chronic sputum production cough and sputum production – cough and sputum production – due to Increased due to Increased

mucus production and reduced mucociliary clearance mucus production and reduced mucociliary clearance Dyspnea:Dyspnea: Progressive and PersistentProgressive and Persistent "increased effort to breathe" "heaviness" "air hunger" "increased effort to breathe" "heaviness" "air hunger"

or "gasping" or "gasping" Worse on exercise Worse on exercise Worse during respiratory infectionsWorse during respiratory infections

HistoryHistory

Most patients seek medical attention Most patients seek medical attention late in the course of their disease. late in the course of their disease. Patients often ignore the symptoms Patients often ignore the symptoms because they start gradually and because they start gradually and progress over the course of years. progress over the course of years. Patients often modify their lifestyle to Patients often modify their lifestyle to minimize dyspnea and ignore cough and minimize dyspnea and ignore cough and phlegm production. With retroactive phlegm production. With retroactive questioning, a multiyear history can be questioning, a multiyear history can be elicited. elicited.

HistoryHistory (con---d) (con---d)

Commonly, patients present in their Commonly, patients present in their fifth decade of life with productive fifth decade of life with productive cough or acute chest illness. The cough or acute chest illness. The cough usually is worse in the cough usually is worse in the morning and produces small morning and produces small amounts of colorless sputum from amounts of colorless sputum from concomitant chronic bronchitis. concomitant chronic bronchitis.

History History (con---d)(con---d)

Breathlessness, the most significant Breathlessness, the most significant symptom, does not occur until the symptom, does not occur until the sixth decade of life. By the time the sixth decade of life. By the time the forced expiratory volume in 1 second forced expiratory volume in 1 second (FEV1) has fallen to 50% of (FEV1) has fallen to 50% of predicted, the patient is breathless predicted, the patient is breathless upon minimal exertion. upon minimal exertion.


Wheezing may occur in some Wheezing may occur in some patients, particularly during exertion patients, particularly during exertion and exacerbations and exacerbations


AAT-deficient patients present earlier than AAT-deficient patients present earlier than other COPD patients. Severe AAT deficiency other COPD patients. Severe AAT deficiency mainly affects the lungs and the liver. Liver mainly affects the lungs and the liver. Liver dysfunction dominates the clinical picture in dysfunction dominates the clinical picture in the first decade of life. The patients who are the first decade of life. The patients who are homozygous (ie, homozygous (ie, PIZZPIZZ) develop emphysema ) develop emphysema with the following distinctive features: early with the following distinctive features: early presentation (<50 y), predilection for the presentation (<50 y), predilection for the lung bases, and panacinar morphological lung bases, and panacinar morphological pattern. pattern.

Key Indicators for COPD Diagnosis

Tobacco smoke (including beedi)occupational dusts and chemical smoke from home cooking and heating fuel

History of exposure to risk factors

Repeated episodesAcute bronchitis

Progressive (worsens over time)Persistent (present every day)Worse on exerciseWorse during respiratory infections

Dyspnoea that is

Present for many years, worst in winters. Initially mucoid – becomes purulent with exacerbation

Chronic sputum production

Present intermittently or every day often present throughout the day; seldom only nocturnal

Chronic cough

Clinical examinationClinical examination Large barrel shaped chest (hyperinflation)Large barrel shaped chest (hyperinflation) Prominent accessory respiratory muscles in neck and Prominent accessory respiratory muscles in neck and

use of accessory muscle in respirationuse of accessory muscle in respiration Low, flat diaphragmLow, flat diaphragm HHyperresonance upon percussion yperresonance upon percussion Diminished breath sound Diminished breath sound Ronchi- in early disease present on forced expiration, Ronchi- in early disease present on forced expiration,

later present in inspiration and expirationlater present in inspiration and expiration Prolonged forced expiratory time (> 6 seconds)Prolonged forced expiratory time (> 6 seconds) Hyperinflation: Hyperinflation: cardiac dullness, liver dullness cardiac dullness, liver dullness

displaced downwards, displaced downwards, A-P chest diameter, A-P chest diameter, heart and heart and breath sounds, Hoover signbreath sounds, Hoover sign

Inspiratory crepitations (lung bases)Inspiratory crepitations (lung bases) Pursed lips breathing ( Pursed lips breathing ( dynamic airway collapse) dynamic airway collapse) Use accessory respiratory musclesUse accessory respiratory muscles Signs of cor pulmonale and PHTSigns of cor pulmonale and PHT

Barrel chestBarrel chest

Emphysema Patient and Emphysema Patient and the Positionthe Position

Clinical examinationClinical examination The sensitivity of the physical evaluation in mild-to-The sensitivity of the physical evaluation in mild-to-

moderate disease is relatively poor. However, the moderate disease is relatively poor. However, the physical signs are quite sensitive and specific for severe physical signs are quite sensitive and specific for severe disease. Patients with severe disease experience disease. Patients with severe disease experience tachypnea and respiratory distress with simple activities.tachypnea and respiratory distress with simple activities.

The respiratory rate increases in proportion to disease The respiratory rate increases in proportion to disease severity. The use of accessory respiratory muscles and severity. The use of accessory respiratory muscles and paradoxical indrawing of lower intercostal spaces are paradoxical indrawing of lower intercostal spaces are evident.evident.

In advanced disease, cyanosis, elevated jugular venous In advanced disease, cyanosis, elevated jugular venous pressure, and peripheral edema can be observed.pressure, and peripheral edema can be observed.

Measurement of the forced expiratory time maneuver is a Measurement of the forced expiratory time maneuver is a simple bedside test; a forced expiratory time greater simple bedside test; a forced expiratory time greater than 6 seconds indicates severe expiratory airflow than 6 seconds indicates severe expiratory airflow obstruction.obstruction.

Emphysema:ChronicBronchitisEmphysema = pink puffer Chronic Bronchitis = blue bloater

Age 60 + y 50 ± y

Rest dyspnea mild-mod none

Exer dyspnea severe moderate

Cough ± prominent

Sputum scanty, mucoid large volume, purulent

Resp infect less often often

Resp failure terminal repeatedly

Cor pulmonale terminal common

PHT (rest) 0-mild Mild-moderate

(exertion) moderate severe

Build Asthenic, cachectic obese, cyanosed

Hematocrit 35-45 50-55

Breath pattern use accessory muscles of respiration do not use accessory muscles of respiration

Sleep pattern Normal sleep apnea

XRC Hyperinflation; Bullae Increased bronchovascular markings

DiagnosisDiagnosis Diagnosis of COPD is based on a history of Diagnosis of COPD is based on a history of

exposure to exposure to risk factors risk factors and the presence of and the presence of airflow limitation that is not fully reversible, airflow limitation that is not fully reversible, with or without the presence of symptoms.with or without the presence of symptoms.

Patients who have chronic cough and sputum Patients who have chronic cough and sputum production with a history of exposure to risk production with a history of exposure to risk factors should be tested for airflow limitation, factors should be tested for airflow limitation, even if they do not have dyspnea.even if they do not have dyspnea.

For the diagnosis and assessment of COPD, For the diagnosis and assessment of COPD, spirometry is the gold standard.spirometry is the gold standard.

Health care workers involved in the diagnosis Health care workers involved in the diagnosis and management of COPD patients should have and management of COPD patients should have access to spirometry.access to spirometry.

SYMPTOMS

coughcoughsputumsputumdyspneadyspnea

EXPOSURE TO RISKFACTORS

tobaccotobaccooccupationoccupation

indoor/outdoor pollutionindoor/outdoor pollution

SPIROMETRYSPIROMETRY

Diagnosis of COPDDiagnosis of COPD

Spirometry to DiagnoseSpirometry to DiagnoseSpirometrySpirometry

FEV1 – Forced expired volume FEV1 – Forced expired volume in the first in the first secondsecond

FVC – FVC – Total volume of air that can be Total volume of air that can be exhaled from maximal inhalation to maximal exhaled from maximal inhalation to maximal exhalationexhalation

FEV1/FVC% - FEV1/FVC% - The ratio of FEV1 to FVC, The ratio of FEV1 to FVC, expressed as a percentage.expressed as a percentage.

FEV1/FVC <70% and a postbronchodilator FEV1/FVC <70% and a postbronchodilator FEV1 <80% predicted confirms the presence FEV1 <80% predicted confirms the presence of airflow limitation that is not fully of airflow limitation that is not fully reversible.reversible.

SpirometrySpirometry

Classification by SeverityClassification by SeverityCOPD classification based on spirometry

GOLD 2003

SPIROMETRY is not to substitute for clinical judgment in the evaluation of the severity of disease in individual patients.

<30<0.7Very severe COPD

30-50<0.7Severe COPD

50-80<0.7Moderate COPD

>80<0.7Mild COPD

>80>0.7At risk

PostbronchodilatorFEV1% predicted

Postbronchodilator FEV1/ FVC

Severity

Spirometry: Normal and COPDSpirometry: Normal and COPD

0

5

1

4

2

3

Lit

er

1 65432

FVC

FVC

FEV1

FEV1

Normal

COPD

3.900

5.200

2.350

4.150 80 %

60 %NormalCOPD

FVCFEV1 FVCFEV1/

Seconds

Laboratory StudiesLaboratory Studies

Arterial blood gas analysis: Patients Arterial blood gas analysis: Patients with mild chronic obstructive with mild chronic obstructive pulmonary disease (COPD) have pulmonary disease (COPD) have mild-to-moderate hypoxemia without mild-to-moderate hypoxemia without hypercapnia. As the disease hypercapnia. As the disease progresses, hypoxemia worsens and progresses, hypoxemia worsens and hypercapnia develops. hypercapnia develops.


Hematocrit value: Chronic hypoxemia Hematocrit value: Chronic hypoxemia may lead polycythemia. A hematocrit may lead polycythemia. A hematocrit value greater than 52% in men and value greater than 52% in men and greater than 47% in women is indicative greater than 47% in women is indicative of the condition. Patients should be of the condition. Patients should be evaluated for hypoxemia at rest, with evaluated for hypoxemia at rest, with exertion, or during sleep. Correction of exertion, or during sleep. Correction of hypoxemia should reduce secondary hypoxemia should reduce secondary polycythemia in patients who have quit polycythemia in patients who have quit smoking. smoking.


Bicarbonate value: Bicarbonate value: Chronic Chronic respiratory acidosisrespiratory acidosis leads to leads to compensatory metabolic alkalosis. In compensatory metabolic alkalosis. In the absence of blood gas the absence of blood gas measurements, bicarbonate levels measurements, bicarbonate levels are useful for following disease are useful for following disease progression. progression.


Alpha1-antitrypsin Alpha1-antitrypsin level: Of the approximately level: Of the approximately 75 different alleles for alpha1-antitrypsin (AAT) 75 different alleles for alpha1-antitrypsin (AAT) deficiency variants, 10-15 are associated with deficiency variants, 10-15 are associated with serum levels below the protective threshold of 11 serum levels below the protective threshold of 11 mmol/L. The most common severe variant is the Z mmol/L. The most common severe variant is the Z allele, which accounts for 95% of the clinically allele, which accounts for 95% of the clinically recognized cases of severe AAT deficiency. The recognized cases of severe AAT deficiency. The diagnosis of severe AAT deficiency is confirmed diagnosis of severe AAT deficiency is confirmed when the serum level falls below the protective when the serum level falls below the protective threshold value (ie, 3-7 mmol/L). Specific threshold value (ie, 3-7 mmol/L). Specific phenotyping is reserved for patients in whom phenotyping is reserved for patients in whom serum levels are 7-11 mmol/L or when genetic serum levels are 7-11 mmol/L or when genetic counseling or family analysis is needed. counseling or family analysis is needed.


Sputum evaluationSputum evaluation: In patients with : In patients with stable chronic bronchitis, the sputum is stable chronic bronchitis, the sputum is mucoid and the predominant cells are mucoid and the predominant cells are macrophages. With an exacerbation, the macrophages. With an exacerbation, the sputum becomes purulent, with excessive sputum becomes purulent, with excessive neutrophils and a mixture of organisms neutrophils and a mixture of organisms visualized through Gram visualized through Gram staining. staining. StreptococcusStreptococcus pneumoniaepneumoniae

and and Haemophilus influenzaeHaemophilus influenzae are pathogens are pathogens frequently cultured during exacerbations. frequently cultured during exacerbations.

Imaging StudiesImaging Studies

CXR CXR shows hyperinflation, flattened diaphragms, increased shows hyperinflation, flattened diaphragms, increased retrosternal space, and hyperlucency of the lung parenchyma in retrosternal space, and hyperlucency of the lung parenchyma in

emphysema.emphysema.

AAn emphysematous lung shows increased anteroposterior n emphysematous lung shows increased anteroposterior (AP) diameter, increased retrosternal airspace, and flattened (AP) diameter, increased retrosternal airspace, and flattened

diaphragms on posteroanteriordiaphragms on posteroanterior (PA) film.(PA) film.

CT scanningCT scanning A CT scan shows emphysematous A CT scan shows emphysematous

bullae in upper lobes.bullae in upper lobes.

CT scanningCT scanning

A CT scan showing severe A CT scan showing severe emphysema and bullous disease.emphysema and bullous disease.

BRONCHIAL ASTHMABRONCHIAL ASTHMA

Asthma is an airway disorder that Asthma is an airway disorder that causes respiratory hypersensitivity, causes respiratory hypersensitivity, inflammation, and intermittent inflammation, and intermittent obstruction. Asthma commonly obstruction. Asthma commonly causes constriction of the smooth causes constriction of the smooth muscles in the airway, wheezing, and muscles in the airway, wheezing, and dyspnea.dyspnea.

BRONCHIAL ASTHMABRONCHIAL ASTHMA

Asthma is a common chronic disorder of Asthma is a common chronic disorder of the airways that is complex and the airways that is complex and characterized by variable and recurring characterized by variable and recurring symptoms, airflow obstruction, symptoms, airflow obstruction, bronchial hyperresponsiveness, and an bronchial hyperresponsiveness, and an underlying inflammation. The underlying inflammation. The interaction of these features of asthma interaction of these features of asthma determines the clinical manifestations determines the clinical manifestations and severity of asthma and the and severity of asthma and the response to treatment.response to treatment.

CausesCauses Environmental allergens: House dust mites, Environmental allergens: House dust mites,

animal allergens (especially cat and dog), animal allergens (especially cat and dog), cockroach allergens, and fungi are most cockroach allergens, and fungi are most commonly reported. commonly reported.

Viral respiratory tract infections Viral respiratory tract infections Exercise; hyperventilation Exercise; hyperventilation Gastroesophageal reflux disease Gastroesophageal reflux disease Chronic sinusitis or rhinitis Chronic sinusitis or rhinitis Aspirin or nonsteroidal anti-inflammatory drug Aspirin or nonsteroidal anti-inflammatory drug

(NSAID) hypersensitivity, sulfite sensitivity (NSAID) hypersensitivity, sulfite sensitivity Use of beta-adrenergic receptor blockers Use of beta-adrenergic receptor blockers

(including ophthalmic preparations) (including ophthalmic preparations) Obesity: Based on a prospective cohort study of Obesity: Based on a prospective cohort study of

86,000 patients, those with an elevated body 86,000 patients, those with an elevated body mass index are more likely to have asthma. mass index are more likely to have asthma.

Environmental pollutants, tobacco smokeEnvironmental pollutants, tobacco smoke

CausesCauses Occupational exposure Occupational exposure Irritants (eg, household sprays, paint fumes) Irritants (eg, household sprays, paint fumes) Various high and low molecular weight Various high and low molecular weight

compounds: A variety of high and low compounds: A variety of high and low molecular weight compounds are associated molecular weight compounds are associated with the development of occupational with the development of occupational asthma, such as insects, plants, latex, gums, asthma, such as insects, plants, latex, gums, diisocyanates, anhydrides, wood dust, and diisocyanates, anhydrides, wood dust, and fluxes. fluxes.

Emotional factors or stress Emotional factors or stress Perinatal factors: Prematurity and increased Perinatal factors: Prematurity and increased

maternal age increase the risk for asthma; maternal age increase the risk for asthma; breastfeeding has not been definitely shown breastfeeding has not been definitely shown to be protective. Both maternal smoking and to be protective. Both maternal smoking and prenatal exposure to tobacco smoke also prenatal exposure to tobacco smoke also increase the risk of developing asthma.increase the risk of developing asthma.

Factors that contribute to exercise-induced Factors that contribute to exercise-induced bronchospasm symptoms (in both people bronchospasm symptoms (in both people

with asthma and athletes) include the with asthma and athletes) include the

following:following:

Exposure to cold or dry air Exposure to cold or dry air Environmental pollutants (eg, sulfur, Environmental pollutants (eg, sulfur,

ozone) ozone) level of bronchial hyperreactivity level of bronchial hyperreactivity Chronicity of asthma and symptomatic Chronicity of asthma and symptomatic

control control Duration and intensity of exercise Duration and intensity of exercise Allergen exposure in atopic individuals Allergen exposure in atopic individuals Coexisting respiratory infectionCoexisting respiratory infection

FrequencyFrequency

Asthma is common in industrialized nations such Asthma is common in industrialized nations such as Canada, England, Australia, Germany, and as Canada, England, Australia, Germany, and New Zealand, where much of the asthma data New Zealand, where much of the asthma data have been collected. The prevalence rate of have been collected. The prevalence rate of severe asthma in industrialized countries ranges severe asthma in industrialized countries ranges from 2-10% and is estimated to affect 300 from 2-10% and is estimated to affect 300 million persons worldwide. Trends suggest an million persons worldwide. Trends suggest an increase in both the prevalence and morbidity of increase in both the prevalence and morbidity of asthma, especially in children younger than 6 asthma, especially in children younger than 6 years. Factors that have been implicated include years. Factors that have been implicated include urbanization, air pollution, passive smoking, and urbanization, air pollution, passive smoking, and change in exposure to environmental allergens.change in exposure to environmental allergens.

Age Age

Asthma prevalence is increased in very Asthma prevalence is increased in very young persons and very old persons young persons and very old persons because of airway responsiveness and because of airway responsiveness and lower levels of lung function.lower levels of lung function. Two thirds Two thirds of all asthma cases are diagnosed before of all asthma cases are diagnosed before the patient is aged 18 years. the patient is aged 18 years. Approximately half of all children Approximately half of all children diagnosed with asthma have a decrease diagnosed with asthma have a decrease or disappearance of symptoms by early or disappearance of symptoms by early adulthood.adulthood.

Age Age

The assessment and diagnosis of The assessment and diagnosis of exercise-induced bronchospasm is exercise-induced bronchospasm is made more often in children and young made more often in children and young adults than in older adults and is related adults than in older adults and is related to high levels of physical activity. to high levels of physical activity. Exercise-induced bronchospasm can be Exercise-induced bronchospasm can be observed in persons of any age based observed in persons of any age based on the level of underlying airway on the level of underlying airway reactivity and the level of physical reactivity and the level of physical exertion. exertion.


The pathophysiology of asthma is The pathophysiology of asthma is complex and involves the following complex and involves the following components:components:

Airway inflammation Airway inflammation Intermittent airflow obstruction Intermittent airflow obstruction Bronchial hyperresponsivenessBronchial hyperresponsiveness


The mechanism of inflammation in asthma The mechanism of inflammation in asthma may be acute, subacute, or chronic, and the may be acute, subacute, or chronic, and the presence of airway edema and mucus presence of airway edema and mucus secretion also contributes to airflow secretion also contributes to airflow obstruction and bronchial reactivity. Varying obstruction and bronchial reactivity. Varying degrees of mononuclear cell and eosinophil degrees of mononuclear cell and eosinophil infiltration, mucus hypersecretion, infiltration, mucus hypersecretion, desquamation of the epithelium, smooth desquamation of the epithelium, smooth muscle hyperplasia, and airway remodeling muscle hyperplasia, and airway remodeling are present are present


Some of the principal cells identified in airway Some of the principal cells identified in airway inflammation include mast cells, eosinophils, inflammation include mast cells, eosinophils, epithelial cells, macrophages, and activated T epithelial cells, macrophages, and activated T lymphocytes. T lymphocytes play an important lymphocytes. T lymphocytes play an important role in the regulation of airway inflammation role in the regulation of airway inflammation through the release of numerous cytokines. Other through the release of numerous cytokines. Other constituent airway cells, such as fibroblasts, constituent airway cells, such as fibroblasts, endothelial cells, and epithelial cells, contribute endothelial cells, and epithelial cells, contribute to the chronicity of the disease. Other factors, to the chronicity of the disease. Other factors, such as adhesion molecules (eg, selectins, such as adhesion molecules (eg, selectins, integrins), are critical in directing the integrins), are critical in directing the inflammatory changes in the airway. Finally, cell-inflammatory changes in the airway. Finally, cell-derived mediators influence smooth muscle tone derived mediators influence smooth muscle tone and produce structural changes and remodeling and produce structural changes and remodeling of the airway of the airway


The presence of airway hyperresponsiveness The presence of airway hyperresponsiveness or bronchial hyperreactivity in asthma is an or bronchial hyperreactivity in asthma is an exaggerated response to numerous exaggerated response to numerous exogenous and endogenous stimuli. The exogenous and endogenous stimuli. The mechanisms involved include direct mechanisms involved include direct stimulation of airway smooth muscle and stimulation of airway smooth muscle and indirect stimulation by pharmacologically indirect stimulation by pharmacologically active substances from mediator-secreting active substances from mediator-secreting cells such as mast cells or nonmyelinated cells such as mast cells or nonmyelinated sensory neurons. The degree of airway sensory neurons. The degree of airway hyperresponsiveness generally correlates hyperresponsiveness generally correlates with the clinical severity of asthma.with the clinical severity of asthma.

The pathogenesis of exercise-induced The pathogenesis of exercise-induced bronchospasm is controversial. The disease may bronchospasm is controversial. The disease may be mediated by water loss from the airway, heat be mediated by water loss from the airway, heat loss from the airway, or a combination of both. loss from the airway, or a combination of both. The upper airway is designed to keep inspired air The upper airway is designed to keep inspired air at 100% humidity and body temperature at 37°C at 100% humidity and body temperature at 37°C (98.6°F). The nose is unable to condition the (98.6°F). The nose is unable to condition the increased amount of air required for exercise, increased amount of air required for exercise, particularly in athletes who breathe through their particularly in athletes who breathe through their mouths. The abnormal heat and water fluxes in mouths. The abnormal heat and water fluxes in the bronchial tree result in bronchoconstriction, the bronchial tree result in bronchoconstriction, occurring within minutes of completing exercise. occurring within minutes of completing exercise. Results from bronchoalveolar lavage studies have Results from bronchoalveolar lavage studies have not demonstrated an increase in inflammatory not demonstrated an increase in inflammatory mediators. These patients generally develop a mediators. These patients generally develop a refractory period, during which a second exercise refractory period, during which a second exercise challenge does not cause a significant degree of challenge does not cause a significant degree of bronchoconstriction.bronchoconstriction.

PathophysiologyPathophysiology Airflow obstruction can be caused by a variety of Airflow obstruction can be caused by a variety of

changes, including acute bronchoconstriction, airway changes, including acute bronchoconstriction, airway edema, chronic mucous plug formation, and airway edema, chronic mucous plug formation, and airway remodeling. Acute bronchoconstriction is the remodeling. Acute bronchoconstriction is the consequence of immunoglobulin E–dependent consequence of immunoglobulin E–dependent mediator release upon exposure to aeroallergens and mediator release upon exposure to aeroallergens and is the primary component of the early asthmatic is the primary component of the early asthmatic response. Airway edema occurs 6-24 hours following response. Airway edema occurs 6-24 hours following an allergen challenge and is referred to as the late an allergen challenge and is referred to as the late asthmatic response. Chronic mucous plug formation asthmatic response. Chronic mucous plug formation consists of an exudate of serum proteins and cell consists of an exudate of serum proteins and cell debris that may take weeks to resolve. Airway debris that may take weeks to resolve. Airway remodeling is associated with structural changes due remodeling is associated with structural changes due to long-standing inflammation and may profoundly to long-standing inflammation and may profoundly affect the extent of reversibility of airway obstruction affect the extent of reversibility of airway obstruction

PhysicalPhysical examination examination

General asthma physical findings General asthma physical findings Evidence of respiratory distress Evidence of respiratory distress

manifests as increased respiratory manifests as increased respiratory rate, increased heart rate, rate, increased heart rate, diaphoresis, and use of accessory diaphoresis, and use of accessory muscles of respiration. muscles of respiration.

Marked weight loss or severe Marked weight loss or severe wasting may indicate severe wasting may indicate severe emphysema.emphysema.


Pulsus paradoxus: This is an Pulsus paradoxus: This is an exaggerated fall in systolic blood exaggerated fall in systolic blood pressure during inspiration and pressure during inspiration and may occur during an acute may occur during an acute asthma exacerbation. asthma exacerbation.

Depressed sensorium: This Depressed sensorium: This finding suggests a more severe finding suggests a more severe asthma exacerbation with asthma exacerbation with impending respiratory failure.impending respiratory failure.

PhysicalPhysical examination examination Chest examination Chest examination End-expiratory wheezing or a prolonged End-expiratory wheezing or a prolonged

expiratory phase is found most commonly, expiratory phase is found most commonly, although inspiratory wheezing can be heard. although inspiratory wheezing can be heard.

Diminished breath sounds and chest Diminished breath sounds and chest hyperinflation (especially in children) may be hyperinflation (especially in children) may be observed during acute asthma observed during acute asthma exacerbations. exacerbations.

The presence of inspiratory wheezing or The presence of inspiratory wheezing or stridor may prompt an evaluation for an stridor may prompt an evaluation for an upper airway obstruction such as vocal cord upper airway obstruction such as vocal cord dysfunction, vocal cord paralysis, thyroid dysfunction, vocal cord paralysis, thyroid enlargement, or a soft tissue mass (eg, enlargement, or a soft tissue mass (eg, malignant tumor).malignant tumor).


Upper airway Upper airway Look for evidence of erythematous or Look for evidence of erythematous or

boggy turbinates or the presence of boggy turbinates or the presence of polyps from sinusitis, allergic rhinitis, or polyps from sinusitis, allergic rhinitis, or upper respiratory tract infection. upper respiratory tract infection.

Any type of nasal obstruction may result Any type of nasal obstruction may result in worsening of asthma or symptoms of in worsening of asthma or symptoms of exercise-induced bronchospasm.exercise-induced bronchospasm.

Skin: Observe for the presence of atopic Skin: Observe for the presence of atopic dermatitis, eczema, or other dermatitis, eczema, or other manifestations of allergic skin manifestations of allergic skin conditions.conditions.

Laboratory Studies Laboratory Studies

Blood eosinophilia greater than 4% or Blood eosinophilia greater than 4% or 300-400/µL supports the diagnosis of 300-400/µL supports the diagnosis of asthma, but an absence of this finding asthma, but an absence of this finding is not exclusionary. Eosinophil counts is not exclusionary. Eosinophil counts greater than 8% may be observed in greater than 8% may be observed in patients with concomitant atopic patients with concomitant atopic dermatitis. This finding should prompt dermatitis. This finding should prompt an evaluation for an evaluation for allergic bronchopulmonary allergic bronchopulmonary aspergillosis, Churg-Strauss syndrome, aspergillosis, Churg-Strauss syndrome, or eosinophilic pneumonia.or eosinophilic pneumonia.

Total serum immunoglobulin E levels Total serum immunoglobulin E levels greater than 100 IU are frequently observed greater than 100 IU are frequently observed in patients experiencing allergic reactions, in patients experiencing allergic reactions, but this finding is not specific for asthma but this finding is not specific for asthma and may be observed in patients with other and may be observed in patients with other conditions (eg, allergic bronchopulmonary conditions (eg, allergic bronchopulmonary aspergillosis, Churg-Strauss syndrome). A aspergillosis, Churg-Strauss syndrome). A normal total serum immunoglobulin E level normal total serum immunoglobulin E level does not exclude the diagnosis of asthma. does not exclude the diagnosis of asthma. Elevated serum IgE levels are required for Elevated serum IgE levels are required for chronic asthma patients to be treated with chronic asthma patients to be treated with omalizumab (Xolair).omalizumab (Xolair).

Imaging Studies Imaging Studies

In most patients with asthma, chest In most patients with asthma, chest radiography findings are normal or may radiography findings are normal or may indicate hyperinflation. Findings may indicate hyperinflation. Findings may help rule out other pulmonary diseases help rule out other pulmonary diseases such as allergic bronchopulmonary such as allergic bronchopulmonary aspergillosis or sarcoidosis, which can aspergillosis or sarcoidosis, which can manifest with symptoms of reactive manifest with symptoms of reactive airway disease. Chest radiography airway disease. Chest radiography should be considered in all patients should be considered in all patients being evaluated for asthma to exclude being evaluated for asthma to exclude other diagnoses. other diagnoses.

Imaging StudiesImaging Studies

Sinus CT scanning may be useful Sinus CT scanning may be useful to help exclude acute or chronic to help exclude acute or chronic sinusitis as a contributing factor. sinusitis as a contributing factor. In patients with chronic sinus In patients with chronic sinus symptoms, CT scanning of the symptoms, CT scanning of the sinuses can also help rule out sinuses can also help rule out chronic sinus disease.chronic sinus disease.

Other Tests Other Tests Allergy skin testing is a useful adjunct in individuals Allergy skin testing is a useful adjunct in individuals

with atopy. Results help guide indoor allergen with atopy. Results help guide indoor allergen mitigation or help diagnose allergic rhinitis mitigation or help diagnose allergic rhinitis symptoms. The allergens that most commonly symptoms. The allergens that most commonly cause asthma are aeroallergens such as house dust cause asthma are aeroallergens such as house dust mites, animal danders, pollens, and mold spores. mites, animal danders, pollens, and mold spores. Two methods are available to test for allergic Two methods are available to test for allergic sensitivity to specific allergens in the environment: sensitivity to specific allergens in the environment: allergy skin tests and blood radioallergosorbent allergy skin tests and blood radioallergosorbent tests (RAST). Allergy immunotherapy may be tests (RAST). Allergy immunotherapy may be beneficial in controlling allergic rhinitis and asthma beneficial in controlling allergic rhinitis and asthma symptoms for some patients. symptoms for some patients.

In patients with asthma and symptoms of In patients with asthma and symptoms of gastroesophageal reflux disease (GERD), 24-hour gastroesophageal reflux disease (GERD), 24-hour pH monitoring can help determine if GERD is a pH monitoring can help determine if GERD is a contributing factor.contributing factor.

Pulmonary function testing Pulmonary function testing (spirometry) (spirometry)

Spirometry assessments should be obtained as Spirometry assessments should be obtained as the primary test to establish the asthma the primary test to establish the asthma diagnosis. Spirometry should be performed prior diagnosis. Spirometry should be performed prior to initiating treatment in order to establish the to initiating treatment in order to establish the presence and determine the severity of baseline presence and determine the severity of baseline airway obstruction.26 Optimally, the initial airway obstruction.26 Optimally, the initial spirometry should also include measurements spirometry should also include measurements before and after inhalation of a short-acting before and after inhalation of a short-acting bronchodilator in all patients in whom the bronchodilator in all patients in whom the diagnosis of asthma is considered. Spirometry diagnosis of asthma is considered. Spirometry measures the forced vital capacity (FVC), the measures the forced vital capacity (FVC), the maximal amount of air expired from the point of maximal amount of air expired from the point of maximal inhalation, and the FEV1. A reduced maximal inhalation, and the FEV1. A reduced ratio of FEV1 to FVC, when compared with ratio of FEV1 to FVC, when compared with predicted values, demonstrates the presence of predicted values, demonstrates the presence of airway obstruction. Reversibility is demonstrated airway obstruction. Reversibility is demonstrated by an increase of 12% and 200 mL after the by an increase of 12% and 200 mL after the administration of a short-acting bronchodilator.administration of a short-acting bronchodilator.

Pulmonary function testing Pulmonary function testing (spirometry)(spirometry)

The assessment and diagnosis of The assessment and diagnosis of asthma cannot be based on asthma cannot be based on spirometry findings alone because spirometry findings alone because many other diseases are associated many other diseases are associated with obstructive spirometry indices. with obstructive spirometry indices.

As a preliminary assessment for As a preliminary assessment for exercise-induced asthma (EIA), or exercise-induced asthma (EIA), or exercise-induced bronchospasm (EIB), exercise-induced bronchospasm (EIB), perform spirometry in all patients perform spirometry in all patients with exercise symptoms to determine with exercise symptoms to determine if any baseline abnormalities (ie, the if any baseline abnormalities (ie, the presence of obstructive or restrictive presence of obstructive or restrictive indices) are present.indices) are present.

Methacholine- or histamine-Methacholine- or histamine-challenge testing challenge testing

Bronchoprovocation testing with either Bronchoprovocation testing with either methacholine or histamine is useful methacholine or histamine is useful when spirometry findings are normal when spirometry findings are normal or near normal, especially in patients or near normal, especially in patients with intermittent or exercise-induced with intermittent or exercise-induced asthma symptoms. asthma symptoms. Bronchoprovocation testing helps Bronchoprovocation testing helps determine if airway hyperreactivity is determine if airway hyperreactivity is present, and a negative test result present, and a negative test result usually excludes the diagnosis of usually excludes the diagnosis of asthma.asthma.

Methacholine- or histamine-Methacholine- or histamine-challenge testingchallenge testing

Trained individuals should perform this Trained individuals should perform this asthma testing in an appropriate facility and asthma testing in an appropriate facility and in accordance with the guidelines of the in accordance with the guidelines of the American Thoracic Society published in American Thoracic Society published in 1999.27 Methacholine is administered in 1999.27 Methacholine is administered in incremental doses up to a maximum dose of incremental doses up to a maximum dose of 16 mg/mL, and a 20% decrease in FEV1, up 16 mg/mL, and a 20% decrease in FEV1, up to the 4 mg/mL level, is considered a positive to the 4 mg/mL level, is considered a positive test result for the presence of bronchial test result for the presence of bronchial hyperresponsiveness. The presence of hyperresponsiveness. The presence of airflow obstruction with an FEV1 less than airflow obstruction with an FEV1 less than 65-70% at baseline is generally an indication 65-70% at baseline is generally an indication to avoid performing the test.to avoid performing the test.

Exercise testingExercise testing

Exercise spirometry is the standard Exercise spirometry is the standard method for assessing patients with method for assessing patients with exercise-induced bronchospasm. exercise-induced bronchospasm. Testing involves 6-10 minutes of Testing involves 6-10 minutes of strenuous exertion at 85-90% of strenuous exertion at 85-90% of predicted maximal heart rate and predicted maximal heart rate and measurement of postexercise measurement of postexercise spirometry for 15-30 minutes. The spirometry for 15-30 minutes. The defined cutoff for a positive test result defined cutoff for a positive test result is a 15% decrease in FEV1 after is a 15% decrease in FEV1 after exercise.exercise.

Exercise testingExercise testing

Exercise testing may be accomplished Exercise testing may be accomplished in 3 different ways, using cycle in 3 different ways, using cycle ergometry, a standard treadmill test, or ergometry, a standard treadmill test, or free running exercise. This method of free running exercise. This method of testing is limited because laboratory testing is limited because laboratory conditions may not subject the patient conditions may not subject the patient to the usual conditions that trigger to the usual conditions that trigger exercise-induced bronchospasm exercise-induced bronchospasm symptoms, and results have a lower symptoms, and results have a lower sensitivity for asthma compared with sensitivity for asthma compared with other methods. other methods.

Eucapnic hyperventilation Eucapnic hyperventilation

Eucapnic hyperventilation with Eucapnic hyperventilation with either cold or dry air is an alternate either cold or dry air is an alternate method of bronchoprovocation method of bronchoprovocation testing. testing.

It has been used to evaluate It has been used to evaluate patients for exercise-induced patients for exercise-induced asthma and has been shown to asthma and has been shown to produce results similar to those of produce results similar to those of methacholine-challenge asthma methacholine-challenge asthma testing.testing.

Peak-flow monitoring Peak-flow monitoring Peak-flow monitoring is designed for Peak-flow monitoring is designed for

ongoing monitoring of patients with asthma ongoing monitoring of patients with asthma because the test is simple to perform and because the test is simple to perform and the results are a quantitative and the results are a quantitative and reproducible measure of airflow obstruction. reproducible measure of airflow obstruction.

It can be used for short-term monitoring, It can be used for short-term monitoring, exacerbation management, and daily long-exacerbation management, and daily long-term monitoring. Peak-flow monitoring term monitoring. Peak-flow monitoring should not be used as a substitute for should not be used as a substitute for spirometry to establish the initial diagnosis spirometry to establish the initial diagnosis of asthma. of asthma.

Results can be used to determine the Results can be used to determine the severity of an exacerbation and to help severity of an exacerbation and to help guide therapeutic decisions as part of an guide therapeutic decisions as part of an asthma action plan.asthma action plan.

Peak-flow monitoringPeak-flow monitoring

Inform the patient that a peak Inform the patient that a peak flow of less than 80% of the flow of less than 80% of the patient's personal best indicates patient's personal best indicates a need for additional medication a need for additional medication and a peak flow below 50% and a peak flow below 50% indicates severe exacerbation.indicates severe exacerbation.

Exhaled nitric oxide Exhaled nitric oxide

Exhaled nitric oxide analysis has been Exhaled nitric oxide analysis has been shown to predict airway inflammation and shown to predict airway inflammation and asthma control; however, it is technically asthma control; however, it is technically more complex and not routinely used in more complex and not routinely used in the monitoring of patients with asthma. the monitoring of patients with asthma.

A prospective, controlled study has shown A prospective, controlled study has shown that when inhaled corticosteroid asthma that when inhaled corticosteroid asthma treatment was adjusted to control the treatment was adjusted to control the fraction of exhaled nitric oxide, as fraction of exhaled nitric oxide, as opposed to controlling the standard opposed to controlling the standard indices of asthma, the cumulative dose of indices of asthma, the cumulative dose of ICS was reduced, with no worsening of the ICS was reduced, with no worsening of the frequency of asthma exacerbationsfrequency of asthma exacerbations

ComplicationsComplications

The most common complications of The most common complications of asthma include pneumonia, asthma include pneumonia, pneumothorax or pneumothorax or pneumomediastinum, and pneumomediastinum, and respiratory failure requiring respiratory failure requiring intubation in severe exacerbations.intubation in severe exacerbations.

ComplicationsComplications

Complications associated with most Complications associated with most medications used for asthma are relatively medications used for asthma are relatively rare. However, in those patients who rare. However, in those patients who require long-term corticosteroid use, require long-term corticosteroid use, complications may include osteoporosis, complications may include osteoporosis, immunosuppression, cataracts, myopathy, immunosuppression, cataracts, myopathy, weight gain, addisonian crisis, thinning of weight gain, addisonian crisis, thinning of skin, easy bruising, avascular necrosis, skin, easy bruising, avascular necrosis, diabetes, and psychiatric disorders diabetes, and psychiatric disorders

PrognosisPrognosis

Approximately half the children diagnosed Approximately half the children diagnosed with asthma in childhood outgrow their with asthma in childhood outgrow their disease by late adolescence or early disease by late adolescence or early adulthood and require no further treatment. adulthood and require no further treatment. Patients with poorly controlled asthma Patients with poorly controlled asthma develop long-term changes over time (ie, develop long-term changes over time (ie, with airway remodeling). This can lead to with airway remodeling). This can lead to chronic symptoms and a significant chronic symptoms and a significant irreversible component to their disease. Many irreversible component to their disease. Many patients who develop asthma at an older age patients who develop asthma at an older age also tend to have chronic symptoms.also tend to have chronic symptoms.

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5. Bronchial Obstruction

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