2169Occupational and Environmental Lung Disease CHAPTER 289

FIGURE 289-2 Acute silicosis. This high-resolution computed tomography scan

shows multiple small nodules consistent with silicosis but also diffuse ground-glass

densities with thickened intralobular and interlobular septa producing polygonal

shapes. This has been referred to as “crazy paving.”

them look “used,” and manufacture and installation of artificial stone

(“faux granite”) kitchen countertops.

Workers heavily exposed through sandblasting in confined spaces,

tunneling through rock with a high quartz content (15–25%), or the

manufacture of abrasive soaps may develop acute silicosis with as little

as 10 months of exposure. The clinical and pathologic features of acute

silicosis are similar to those of pulmonary alveolar proteinosis (Chap.

293). The chest radiograph may show profuse miliary infiltration or

consolidation, and there is a characteristic HRCT pattern known as

“crazy paving” (Fig. 289-2). The disease may be quite severe and progressive despite the discontinuation of exposure. Whole-lung lavage

may provide symptomatic relief and slow the progression.

With long-term, less intense exposure, small rounded opacities in

the upper lobes may appear on the chest radiograph after 15–20 years

of exposure, usually without associated impairment of lung function

(simple silicosis). Calcification of hilar nodes may occur in as many

as 20% of cases and produces a characteristic “eggshell” pattern. Silicotic nodules may be identified more readily by HRCT (Fig. 289-3).

The nodular fibrosis may be progressive in the absence of further

exposure, with coalescence and formation of nonsegmental conglomerates of irregular masses >1 cm in diameter (complicated silicosis).

These masses can become quite large, and when this occurs, the term

progressive massive fibrosis (PMF) is applied. Significant functional

impairment with both restrictive and obstructive components may be

associated with PMF.

Because silica causes alveolar macrophage dysfunction, patients

with silicosis are at greater risk of acquiring lung infections that

involve these cells as a primary defense (Mycobacterium tuberculosis,

atypical mycobacteria, and fungi). Because of the increased risk of

active tuberculosis, the recommended treatment of latent tuberculosis

in these patients is longer. Silica has immunoadjuvant properties, and

another potential clinical complication of silicosis is autoimmune

connective tissue disorders such as rheumatoid arthritis and scleroderma. In addition, there are sufficient epidemiologic data that the

International Agency for Research on Cancer lists silica as a probable

lung carcinogen.

Other, less hazardous silicates include fuller’s earth, kaolin, mica,

diatomaceous earths, silica gel, soapstone, carbonate dusts, and cement

dusts. The production of fibrosis in workers exposed to these agents is

believed to be related either to the free silica content of these dusts or,

for substances that contain no free silica, to the potentially large dust

loads to which these workers may be exposed. Some silicates, including

talc and vermiculite, may be contaminated with asbestos. Fibrosis of

lung or pleura, lung cancer, and mesothelioma have been associated

with chronic exposure to talc and vermiculite dusts.

■ COAL WORKER’S PNEUMOCONIOSIS (CWP)

Occupational exposure to coal dust can lead to CWP, which has enormous social, economic, and medical significance in every nation in

which coal mining is an important industry. Simple radiographically

identified CWP is seen in ~10% of all coal miners and in as many as

50% of anthracite miners with >20 years of work on the coal face. The

prevalence of disease is lower in workers in bituminous coal mines.

With prolonged exposure to coal dust (i.e., 15–20 years), small,

rounded opacities similar to those of silicosis may develop. As in silicosis, the presence of these nodules (simple CWP) usually is not associated with pulmonary impairment. In addition to CWP, coal dust can

cause chronic bronchitis and COPD (Chap. 292). The effects of coal

dust are additive to those of cigarette smoking.

Complicated CWP is manifested by the appearance on the chest

radiograph of nodules ≥1 cm in diameter generally confined to the

upper half of the lungs. As in silicosis, this condition can progress to

PMF that is accompanied by severe lung function deficits and associated with premature mortality. Despite improvements in technology to

protect coal miners, cases of PMF still occur in the United States at a

disturbing rate.

FIGURE 289-3 Chronic silicosis. A. Frontal chest radiograph in a patient with

silicosis shows variably sized, poorly defined nodules (arrows) predominating in the

upper lobes. B. Axial thoracic computed tomography image through the lung apices

shows numerous small nodules, more pronounced in the right upper lobe. A number

of the nodules are subpleural in location (arrows).

2170 PART 7 Disorders of the Respiratory System

Caplan syndrome (Chap. 358), first described in coal miners but

subsequently in patients with silicosis, is the combination of pneumoconiotic nodules and seropositive rheumatoid arthritis. Silica is often

present in anthracitic coal dust, and its presence may contribute to risk

of PMF.

■ CHRONIC BERYLLIUM DISEASE

Beryllium is a lightweight metal with tensile strength, good electrical

conductivity, and value in the control of nuclear reactions through

its ability to quench neutrons. Although beryllium may produce an

acute pneumonitis, it is far more commonly associated with a chronic

granulomatous inflammatory disease that is similar to sarcoidosis

(Chap. 367). Unless one inquires specifically about occupational

exposures to beryllium in the manufacture of alloys, ceramics, or hightechnology electronics in a patient with sarcoidosis, one may miss

entirely the etiologic relationship to the occupational exposure. What

distinguishes CBD from sarcoidosis is evidence of a specific cell-mediated immune response (i.e., delayed hypersensitivity) to beryllium.

The test that usually provides this evidence is the beryllium lymphocyte proliferation test (BeLPT). The BeLPT compares the in vitro proliferation of lymphocytes from blood or bronchoalveolar lavage in the

presence of beryllium salts with that of unstimulated cells. Proliferation

is usually measured by lymphocyte uptake of radiolabeled thymidine.

Chest imaging findings are similar to those of sarcoidosis (nodules

along septal lines) except that hilar adenopathy is somewhat less common. As with sarcoidosis, pulmonary function test results may show

restrictive and/or obstructive ventilatory deficits and decreased diffusing capacity. With early disease, both chest imaging studies and pulmonary function tests may be normal. Fiberoptic bronchoscopy with

transbronchial lung biopsy usually is required to make the diagnosis of

CBD. In a beryllium-sensitized individual, the presence of noncaseating granulomas or monocytic infiltration in lung tissue establishes the

diagnosis. Accumulation of beryllium-specific CD4+ T cells occurs in

the granulomatous inflammation seen on lung biopsy. Susceptibility to

CBD is highly associated with human leukocyte antigen DP (HLA-DP)

alleles that have a glutamic acid in position 69 of the β chain.

■ OTHER METALS

Aluminum and titanium dioxide have been rarely associated with a sarcoid-like reaction in lung tissue. Exposure to dust containing tungsten

carbide, also known as “hard metal,” may produce giant cell interstitial

pneumonitis. Cobalt is a constituent of tungsten carbide and is the

likely etiologic agent of both the interstitial pneumonitis and the occupational asthma that may occur. The most common exposures to tungsten carbide occur in tool and dye, saw blade, and drill bit manufacture.

Diamond polishing may also involve exposure to cobalt dust. In

patients with interstitial lung disease, one should always inquire about

exposure to metal fumes and/or dusts. Especially when sarcoidosis

appears to be the diagnosis, one should always consider possible CBD.

■ OTHER INORGANIC DUSTS

Most of the inorganic dusts discussed thus far are associated with the

production of either dust macules or interstitial fibrotic changes in the

lung. Other inorganic and organic dusts (see categories in Table 289-1),

along with some of the dusts previously discussed, are associated with

chronic mucus hypersecretion (chronic bronchitis), with or without

reduction of expiratory flow rates. Cigarette smoking is the major

cause of these conditions, and any effort to attribute some component

of the disease to occupational and environmental exposures must take

cigarette smoking into account. Most studies suggest an additive effect

of dust exposure and smoking. The pattern of the irritant dust effect

is similar to that of cigarette smoking, suggesting that small airway

inflammation may be the initial site of pathologic response in those

cases and continued exposure may lead to chronic bronchitis and

COPD.

■ ORGANIC DUSTS

Some of the specific diseases associated with organic dusts are discussed in detail in the chapters on asthma (Chap. 287) and hypersensitivity pneumonitis (Chap. 288). Many of these diseases are named

for the specific setting in which they are found, e.g., farmer’s lung, malt

worker’s disease, and mushroom worker’s disease. Often the temporal

relation of symptoms to exposure furnishes the best evidence for the

diagnosis. Three occupational exposures are singled out for discussion

here because they affect the largest proportions of workers.

Cotton Dust (Byssinosis) Workers occupationally exposed to

cotton dust (but also to flax, hemp, or jute dust) in the production of

yarns for textiles and rope making are at risk for an asthma-like syndrome known as byssinosis. The risk of byssinosis is associated with

both cotton dust and endotoxin levels in the workplace environment.

Byssinosis is characterized clinically as occasional (early-stage) and

then regular (late-stage) chest tightness toward the end of the first day

of the workweek (“Monday chest tightness”). Exposed workers may

show a significant drop in FEV1

 over the course of a Monday workshift. Initially the symptoms do not recur on subsequent days of the

week, but in a subset of workers, chest tightness may recur or persist

throughout the workweek. After >10 years of exposure, workers with

recurrent symptoms are more likely to have an obstructive pattern on

pulmonary function testing.

Dust exposure can be reduced by the use of exhaust hoods, general increases in ventilation, and wetting procedures, but respiratory

protective equipment may be required during certain operations.

Regular surveillance of pulmonary function in cotton dust–exposed

workers using spirometry before and after the workshift is required by

OSHA. All workers with persistent symptoms or significantly reduced

levels of pulmonary function should be moved to areas of lower risk

of exposure.

Grain Dust Worldwide, many farmers and workers in grain storage

facilities are exposed to grain dust. The presentation of obstructive

airway disease in grain dust–exposed workers is virtually identical to

the characteristic findings in cigarette smokers, i.e., persistent cough,

mucus hypersecretion, wheeze and dyspnea on exertion, and reduced

FEV1

 and FEV1

/FVC (forced vital capacity) ratio (Chap. 285).

Dust concentrations in grain elevators vary greatly but can be

>10,000 μg/m3

 with many particles in the respirable size range. The

effect of grain dust exposure is additive to that of cigarette smoking,

with ~50% of workers who smoke having symptoms. Smoking grain

dust–exposed workers are more likely to have obstructive ventilatory

deficits on pulmonary function testing. As in byssinosis, endotoxin

may play a role in grain dust–induced chronic bronchitis and COPD.

Farmer’s Lung This condition results from exposure to moldy hay

containing spores of thermophilic actinomycetes that produce a hypersensitivity pneumonitis (Chap. 288). A patient with acute farmer’s

lung presents 4–8 h after exposure with fever, chills, malaise, cough,

and dyspnea without wheezing. The history of exposure is obviously

essential to distinguish this disease from influenza or pneumonia with

similar symptoms. In the chronic form of the disease, the history of

repeated attacks after similar exposure is important in differentiating

this syndrome from other causes of patchy fibrosis (e.g., sarcoidosis).

A wide variety of other organic dusts are associated with the occurrence of hypersensitivity pneumonitis (Chap. 288). For patients who

present with hypersensitivity pneumonitis, specific and careful inquiry

about occupations, hobbies, and other home environmental exposures

is necessary to uncover the source of the etiologic agent.

■ TOXIC CHEMICALS

Exposure to toxic chemicals affecting the lung generally involves gases

and vapors. A common accident is one in which the victim is trapped

in a confined space where the chemicals have accumulated to harmful

levels. In addition to the specific toxic effects of the chemical, the victim often sustains considerable anoxia, which can play a dominant role

in determining whether the individual survives.

Table 289-2 lists a variety of toxic agents that can produce acute

and sometimes life-threatening reactions in the lung. All these agents

in sufficient concentrations have been demonstrated, at least in animal

studies, to affect the lower airways and disrupt alveolar architecture,

either acutely or as a result of chronic exposure.

2171Occupational and Environmental Lung Disease CHAPTER 289

Firefighters and fire victims are at risk of smoke inhalation, an

important cause of acute cardiorespiratory failure. Smoke inhalation

kills more fire victims than does thermal injury. Carbon monoxide

poisoning with resulting significant hypoxemia can be life-threatening

(Chap. 459). Synthetic materials (plastic, polyurethanes), when

burned, may release a variety of other toxic agents (such as cyanide and

hydrochloric acid), and this must be considered in evaluating smoke

inhalation victims. Exposed victims may have some degree of lower

respiratory tract inflammation and/or pulmonary edema.

Exposure to certain highly reactive, low-molecular-weight agents

used in the manufacture of synthetic polymers, paints, and coatings

(diisocyanates in polyurethanes, aromatic amines and acid anhydrides

in epoxies) is associated with a high risk of occupational asthma.

Although this occupational asthma manifests clinically as if sensitization has occurred, an IgE antibody–mediated mechanism is not necessarily involved. Hypersensitivity pneumonitis–like reactions also have

been described in diisocyanate and acid anhydride–exposed workers.

Fluoropolymers such as Teflon, which at normal temperatures

produce no reaction, become volatilized upon heating. The inhaled

agents cause a characteristic syndrome of fever, chills, malaise, and

occasionally mild wheezing, leading to the diagnosis of polymer fume

fever. A similar self-limited, influenza-like syndrome—metal fume

fever—results from acute exposure to fumes containing zinc oxide,

typically from welding of galvanized steel. These inhalational fever

syndromes may begin several hours after work and resolve within

24 h, only to return on repeated exposure.

Two other agents have been associated with potentially severe lung

disease. Occupational exposure to nylon flock has been shown to

induce a lymphocytic bronchiolitis, and workers exposed to diacetyl,

which is used to provide “butter” flavor in the manufacture of microwave popcorn and other foods, have developed bronchiolitis obliterans

(Chap. 293).

World Trade Center Disaster A consequence of the attack on

the World Trade Center (WTC) on September 11, 2001, was relatively

heavy exposure of a large number of firefighters and other rescue

workers to the dust generated by the collapse of the buildings. Environmental monitoring and chemical characterization of WTC dust

have revealed a wide variety of potentially toxic constituents, although

much of the dust was pulverized cement. Possibly because of the high

alkalinity of WTC dust, significant cough, wheeze, and phlegm production occurred among firefighters and cleanup crews. New cough

and wheeze syndromes also occurred among local residents. Heavier

exposure to WTC dust among New York City firefighters was associated with accelerated decline of lung function over the first year after

the disaster. More recently, concerns have been raised about risk of

interstitial lung disease, especially of a granulomatous nature.

■ OCCUPATIONAL RESPIRATORY CARCINOGENS

Exposures at work have been estimated to contribute to 10% of all lung

cancer cases. In addition to asbestos, other agents either proven or

suspected to be respiratory carcinogens include acrylonitrile, arsenic

TABLE 289-2 Selected Common Toxic Chemical Agents That Affect the Lung

AGENT(S) SELECTED EXPOSURES

ACUTE EFFECTS FROM HIGH OR

ACCIDENTAL EXPOSURE

CHRONIC EFFECTS FROM RELATIVELY

LOW EXPOSURE

Acid anhydrides Manufacture of resin esters, polyester resins,

thermoactivated adhesives

Nasal irritation, cough Asthma, chronic bronchitis,

hypersensitivity pneumonitis

Acid fumes: H2

SO4

, HNO3 Manufacture of fertilizers, chlorinated organic

compounds, dyes, explosives, rubber products, metal

etching, plastics

Mucous membrane irritation, followed

by chemical pneumonitis 2–3 days later

Bronchitis and suggestion of mildly

reduced pulmonary function in children

with lifelong residential exposure to

high levels

Acrolein and other

aldehydes

By-product of burning plastics, woods, tobacco

smoke

Mucous membrane irritant, decrease in

lung function

Upper respiratory tract irritation

Ammonia Refrigeration; petroleum refining; manufacture of

fertilizers, explosives, plastics, and other chemicals

Same as for acid fumes, but

bronchiectasis also has been reported

Upper respiratory tract irritation,

chronic bronchitis

Cadmium fumes Smelting, soldering, battery production Mucous membrane irritant, acute

respiratory distress syndrome (ARDS)

Chronic obstructive pulmonary disease

(COPD)

Formaldehyde Manufacture of resins, leathers, rubber, metals, and

woods; laboratory workers, embalmers; emission

from urethane foam insulation

Same as for acid fumes Nasopharyngeal cancer

Halides and acid salts

(Cl, Br, F)

Bleaching in pulp, paper, textile industry;

manufacture of chemical compounds; synthetic

rubber, plastics, disinfectant, rocket fuel, gasoline

Mucous membrane irritation, pulmonary

edema; possible reduced forced vital

capacity (FVC) 1–2 years after exposure

Upper respiratory tract irritation,

epistaxis, tracheobronchitis

Hydrogen sulfide By-product of many industrial processes, oil, other

petroleum processes and storage

Increase in respiratory rate followed

by respiratory arrest, lactic acidosis,

pulmonary edema, death

Conjunctival irritation, chronic

bronchitis, recurrent pneumonitis

Isocyanates (TDI, HDI,

MDI)

Production of polyurethane foams, plastics,

adhesives, surface coatings

Mucous membrane irritation, dyspnea,

cough, wheeze, pulmonary edema

Upper respiratory tract irritation, cough,

asthma, hypersensitivity pneumonitis,

reduced lung function

Nitrogen dioxide Silage, metal etching, explosives, rocket fuels,

welding, by-product of burning fossil fuels

Cough, dyspnea, pulmonary edema may

be delayed 4–12 h; possible result from

acute exposure: bronchiolitis obliterans

in 2–6 weeks

Emphysema in animals, chronic

bronchitis, associated with reduced

lung function growth in children with

lifelong residential exposure

Ozone Arc welding, flour bleaching, deodorizing, emissions

from copying equipment, photochemical air pollutant

Mucous membrane irritant, reduced

pulmonary function transiently

in children and adults, asthma

exacerbation

Excess cardiopulmonary mortality rates,

increased risk for new-onset asthma in

children

Phosgene Organic compound, metallurgy, volatilization of

chlorine-containing compounds

Delayed onset of bronchiolitis and

pulmonary edema

Chronic bronchitis

Sulfur dioxide Manufacture of sulfuric acid, bleaches, coating of

nonferrous metals, food processing, refrigerant,

burning of fossil fuels, wood pulp industry

Mucous membrane irritant, epistaxis,

bronchospasm (especially in people

with asthma)

Chronic bronchitis

Abbreviations: HDI, hexamethylene diisocyanate; MDI, methylene diphenyl diisocyanate; TDI, toluene diisocyanate.

2172 PART 7 Disorders of the Respiratory System

compounds, beryllium, bis(chloromethyl) ether, chromium (hexavalent), formaldehyde (nasal), isopropanol (nasal sinuses), mustard gas,

nickel carbonyl (nickel smelting), polycyclic aromatic hydrocarbons

(coke oven emissions and diesel exhaust), secondhand tobacco smoke,

silica (both mining and processing), talc (possible asbestos contamination in both mining and milling), vinyl chloride (sarcomas), wood

(nasal), and uranium. Workers at risk of radiation-related lung cancer

include not only those involved in mining or processing uranium but

also those exposed in underground mining operations of other ores

where radon daughters may be emitted from rock formations.

■ ASSESSMENT OF DISABILITY

Disability is the term used to describe the decreased ability to work due

to the effects of a medical condition. Physicians are generally able to

assess physiologic dysfunction, or impairment, but the rating of disability for compensation of loss of income also involves nonmedical factors

such as the education and employability of the individual. The disability rating scheme differs with the compensation-granting agency. For

example, the U.S. Social Security Administration requires that an individual be unable to do any work (i.e., total disability) before he or she

will receive income replacement payments. Many state workers’ compensation systems allow for payments for partial disability. In the Social

Security scheme, no determination of cause is done, whereas workrelatedness must be established in workers’ compensation systems.

For respiratory impairment rating, resting pulmonary function tests

(spirometry and diffusing capacity) are used as the initial assessment

tool, with cardiopulmonary exercise testing (to assess maximal oxygen

consumption) used if the results of the resting tests do not correlate

with the patient’s symptoms. Methacholine challenge (to assess airway

reactivity) can also be useful in patients with asthma who have normal

spirometry when evaluated. Some compensation agencies (e.g., Social

Security) have proscribed disability classification schemes based on

pulmonary function test results. When no specific scheme is proscribed,

the Guidelines of the American Medical Association should be used.

GENERAL ENVIRONMENTAL EXPOSURES

■ OUTDOOR AIR POLLUTION

Primary standards regulated by the U.S. Environmental Protection

Agency (EPA) designed to protect the public health with an adequate

margin of safety exist for sulfur dioxide, particulate matter (PM), nitrogen dioxide, ozone, lead, and carbon monoxide. Standards for each

of these pollutants are updated regularly through an extensive review

process conducted by the EPA. (For details on current standards, go to

https://www.epa.gov/criteria-air-pollutants/naaqs-table).

Pollutants are generated from both stationary sources (power plants

and industrial facilities) and mobile sources (motor vehicles), and

none of the regulated pollutants occurs in isolation. Furthermore,

pollutants may be changed by chemical reactions after being emitted.

For example, sulfur dioxide and PM emissions from a coal-fired power

plant may react in air to produce acid sulfate aerosols, which can be

transported long distances in the atmosphere. Oxides of nitrogen and

volatile organic compounds from automobile exhaust react with sunlight to produce ozone. Although originally recognized in Los Angeles,

photochemically derived pollution (“smog”) is now known to be a

problem throughout the United States and in many other countries.

Both acute and chronic effects of pollutant exposures have been documented in large population studies.

The symptoms and diseases associated with air pollution are the

same as conditions commonly associated with cigarette smoking. In

addition, decreased growth of lung function and asthma have been

associated with chronic exposure to only modestly elevated levels of

traffic-related air pollution. Multiple population-based time-series

studies within cities have demonstrated excess health care utilization

for asthma and other cardiopulmonary conditions as well as increased

mortality rates. Cohort studies comparing cities that have relatively

high levels of particulate exposures with less polluted communities

suggest excess morbidity and mortality rates from cardiopulmonary conditions in long-term residents of the former. The strong

epidemiologic evidence that fine PM is a risk factor for cardiovascular

morbidity and mortality has prompted toxicologic investigations into

the underlying mechanisms. The inhalation of fine particles from combustion sources generates oxidative stress followed by local injury and

inflammation in the lungs that in turn lead to autonomic and systemic

inflammatory responses. Recent research findings on the health effects

of air pollutants have led to stricter U.S. ambient air quality standards

for ozone, oxides of nitrogen, and PM as well as greater emphasis on

publicizing pollution alerts to encourage individuals with cardiovascular and respiratory disorders to stay indoors during high-pollution

episodes (e.g., from wildfires).

■ INDOOR EXPOSURES

Secondhand tobacco smoke (Chap. 454), radon gas, wood smoke, and

other biologic agents generated indoors must be considered. Several

studies have shown that the respirable particulate load in any household is directly proportional to the number of cigarette smokers living

in that home. Increases in prevalence of respiratory illnesses, especially

asthma, and reduced levels of pulmonary function have been found

in the children of smoking parents in a number of studies. Recent

meta-analyses for lung cancer and cardiopulmonary diseases, combining data from multiple secondhand tobacco smoke epidemiologic

studies, suggest an ~25% increase in relative risk for each condition,

even after adjustment for major potential confounders.

Exposure to radon gas in homes is a risk factor for lung cancer. The

main radon product (radon-222) is a gas that results from the decay series

of uranium-238, with the immediate precursor being radium-226. The

amount of radium in earth materials determines how much radon gas

will be emitted. Levels associated with excess lung cancer risk may be

present in as many as 10% of the houses in the United States. When

smokers reside in the home, the problem is potentially greater, because

the molecular size of radon particles allows them to attach readily to

smoke particles that are inhaled. Fortunately, technology is available for

assessing and reducing the level of exposure.

Other indoor exposures of concern are bioaerosols that contain

antigenic material (fungi, cockroaches, dust mites, and pet danders)

associated with an increased risk of atopy and asthma. Indoor chemical

agents include strong cleaning agents (bleach, ammonia), formaldehyde, perfumes, pesticides, and oxides of nitrogen from gas appliances.

Nonspecific responses associated with “tight-building syndrome,” perhaps better termed “building-associated illness,” in which no particular

agent has been implicated, have included a wide variety of complaints,

among them respiratory symptoms that are relieved only by avoiding

exposure in the building in question. The degree to which “smells”

and other sensory stimuli are involved in the triggering of potentially

incapacitating psychological or physical responses has yet to be determined, and the long-term consequences of such environmental exposures are unknown.

Indoor exposure to household air pollution from cooking or heating

with solid fuels (wood, dung, crop residues, charcoal, coal) is estimated

to be responsible for ~2.7% of worldwide disability-adjusted life-years

(DALYs) lost, due to acute lower respiratory infections in children,

COPD and lung cancer in women, and cardiovascular disease among

men. This burden of disease places exposure to household air pollution

as one of the leading environmental hazards for poor health on a global

scale.

Forty percent of the world’s population uses solid fuel for cooking,

heating, or baking. Kerosene (similar to diesel fuel) is often used for

lighting and sometimes cooking. This occurs predominantly in the

rural areas of developing countries. Because many families burn coal

or biomass fuels in open stoves, which are highly inefficient, and inside

homes with poor ventilation, women and young children are exposed

on a daily basis to high levels of smoke. In these homes, 24-h mean

levels of fine PM have been reported to be 2–30 times higher than the

National Ambient Air Quality Standard set by the U.S. EPA.

Epidemiologic studies have consistently shown associations between

exposure to biomass smoke and both chronic bronchitis and COPD.

Because of increased migration to the United States from developing

countries, clinicians need to be aware of the chronic respiratory effects

2173Bronchiectasis CHAPTER 290

FIGURE 289-4 Histopathologic features of biomass smoke–induced interstitial lung disease. A. Anthracitic pigment is seen accumulating along alveolar septae

(arrowheads) and within a pigmented dust macule (single arrow). B. A high-power photomicrograph contains a mixture of fibroblasts and carbon-laden macrophages.

of exposure to biomass smoke, which can include interstitial lung

disease (Fig. 289-4). Evidence is beginning to emerge that improved

stoves that reduce biomass smoke exposure can reduce risk of respiratory illness in both children and adults.

Household air pollution (HAP) from domestic use of solid fuels

also contributes substantially to outdoor air pollution. Contributions

from HAP, coal-fired power plants without emission scrubbers, and

increased traffic congestion involving motor vehicles without pollution controls can lead to high concentrations of outdoor air pollution,

especially fine PM, in mega-cities in developing countries (e.g., Delhi).

Acknowledgment

The author acknowledges the contribution of Dr. Frank Speizer to the

prior version of this chapter.

■ FURTHER READING

Almberg KS et al: Progressive massive fibrosis resurgence identified in

U.S. coal miners filing for Black Lung Benefits, 1970-2016. Ann Am

Thorac Soc 15:1420, 2018.

Balmes JR: Household air pollution from domestic combustion of

solid fuels and health. J Allergy Clin Immunol 143:1979, 2019.

Blanc PD et al: The occupational burden of nonmalignant respiratory

diseases. An official American Thoracic Society and European Respiratory Society statement. Am J Respir Crit Care Med 199:1312, 2019.

Gauderman WJ et al: Association of improved air quality with lung

development in children. N Engl J Med 372:905, 2015.

Leon-Jimenez A et al: Artificial stone silicosis: Rapid progression following exposure cessation. Chest 158:1060, 2020.

Musk AW et al: Asbestos-related diseases. Int J Tuberc Lung Dis

24:562, 2020.

Bronchiectasis refers to an irreversible airway dilation that involves the

lung in either a focal or a diffuse manner and that classically has been

categorized as cylindrical or tubular (the most common form), varicose, or cystic. This chapter will focus largely on non–cystic fibrosis

(CF) bronchiectasis. The reader is referred to Chapter 291 for a more

focused discussion on CF bronchiectasis.

290 Bronchiectasis

Rebecca M. Baron, Beverly W. Baron,

Miriam Baron Barshak

■ ETIOLOGY

Bronchiectasis can arise from infectious or noninfectious causes

(Table 290-1). Clues to the underlying etiology often are provided

by the pattern of lung involvement. Focal bronchiectasis refers to

bronchiectatic changes in a localized area of the lung and can be a

consequence of obstruction of the airway—either extrinsic (e.g., due

to compression by adjacent lymphadenopathy or parenchymal tumor

mass) or intrinsic (e.g., due to an airway tumor or aspirated foreign

body, a scarred/stenotic airway, or bronchial atresia from congenital

underdevelopment of the airway). Diffuse bronchiectasis is characterized by widespread bronchiectatic changes throughout the lung and

often arises from an underlying systemic or infectious disease process.

More pronounced involvement of the upper lung fields is most

common in CF and also is observed in postradiation fibrosis, corresponding to the lung region encompassed by the radiation port.

Bronchiectasis with predominant involvement of the lower lung fields

usually has its source in chronic recurrent aspiration (e.g., due to

esophageal motility disorders like those in scleroderma), end-stage

fibrotic lung disease (e.g., traction bronchiectasis from idiopathic

pulmonary fibrosis), or recurrent immunodeficiency-associated infections (e.g., hypogammaglobulinemia). Bronchiectasis resulting from

infection by nontuberculous mycobacteria (NTM), most commonly

the Mycobacterium avium-intracellulare complex (MAC), often preferentially affects the midlung fields. Congenital causes of bronchiectasis

with predominant midlung field involvement include the dyskinetic/

immotile cilia syndrome. Finally, predominant involvement of the

central airways is reported in association with allergic bronchopulmonary aspergillosis (ABPA), in which an immune-mediated reaction to

Aspergillus damages the bronchial wall. Congenital causes of central

airway–predominant bronchiectasis resulting from cartilage deficiency include tracheobronchomegaly (Mounier-Kuhn syndrome) and

Williams-Campbell syndrome.

In many cases, the etiology of bronchiectasis is not determined. In

case series, as many as 25–50% of patients referred for bronchiectasis

have idiopathic disease.

■ EPIDEMIOLOGY

The overall reported prevalence of bronchiectasis in the United States

has recently increased, but the epidemiology of bronchiectasis varies

greatly with the underlying etiology. For example, patients born with

CF often develop significant clinical bronchiectasis in late adolescence

or early adulthood, although atypical presentations of CF in adults in

their thirties and forties are also possible. In contrast, bronchiectasis

resulting from MAC infection classically affects nonsmoking women

>50 years of age. In general, the incidence of bronchiectasis increases

with age. Bronchiectasis is more common among women than among

men. Bronchiectasis may also frequently be co-diagnosed with chronic

obstructive pulmonary disease (COPD) or asthma.

2174 PART 7 Disorders of the Respiratory System

significant airway damage and poor secretion clearance. The presence

of the microbes incites continued chronic inflammation, with consequent damage to the airway wall, continued impairment of secretions

and microbial clearance, and ongoing propagation of the infectious/

inflammatory cycle. Moreover, it has been proposed that mediators released directly from bacteria can interfere with mucociliary

clearance.

Classic studies of the pathology of bronchiectasis from the 1950s

demonstrated significant small-airway wall inflammation and

larger-airway wall destruction as well as dilation, with loss of elastin,

smooth muscle, and cartilage. It has been proposed that inflammatory

cells in the small airways release proteases and other mediators, such as

reactive oxygen species and proinflammatory cytokines, that damage

the larger airway walls. Furthermore, the ongoing inflammatory process in the smaller airways results in airflow obstruction. It is thought

that antiproteases, such as α1

 antitrypsin, play an important role in neutralizing the damaging effects of neutrophil elastase and in enhancing

bacterial killing. Bronchiectasis and emphysema have been observed in

patients with α1

 antitrypsin deficiency.

Proposed mechanisms for noninfectious bronchiectasis include

immune-mediated reactions that damage the bronchial wall (e.g., those

associated with systemic autoimmune conditions such as Sjögren’s syndrome and rheumatoid arthritis). Recent studies suggest that there might

exist a new bronchiectasis endophenotype of patients with sensitization

to multiple environmental allergens. Traction bronchiectasis refers to

dilated airways arising from parenchymal distortion as a result of lung

fibrosis (e.g., postradiation fibrosis or idiopathic pulmonary fibrosis).

■ CLINICAL MANIFESTATIONS

The most common clinical presentation is a persistent productive cough

with ongoing production of thick, tenacious sputum. Physical findings

frequently include crackles and wheezing on lung auscultation, and

some patients with bronchiectasis exhibit clubbing of the digits. Mild to

moderate airflow obstruction often is detected on pulmonary function

tests, overlapping with that seen at presentation with other conditions,

such as COPD. Acute exacerbations of bronchiectasis usually are

characterized by changes in the nature of sputum production, with

increased volume and purulence. However, typical signs and symptoms

of lung infection, such as fever and new infiltrates, may not be present.

■ DIAGNOSIS

The diagnosis usually is based on presentation with a persistent

chronic cough and sputum production accompanied by consistent

radiographic features. Although chest radiographs lack sensitivity, the

presence of “tram tracks” indicating dilated airways is consistent with

bronchiectasis. Chest CT is more specific for bronchiectasis and is the

imaging modality of choice for confirming the diagnosis. CT findings

include airway dilation (detected as parallel “tram tracks” or as the

“signet-ring sign”—a cross-sectional area of the airway with a diameter

at least 1.5 times that of the adjacent vessel), lack of bronchial tapering

(including the presence of tubular structures within 1 cm from the

pleural surface), bronchial wall thickening in dilated airways, inspissated secretions (e.g., the “tree-in-bud” pattern), or cysts emanating

from the bronchial wall (especially pronounced in cystic bronchiectasis) (Fig. 290-1).

APPROACH TO THE PATIENT

Bronchiectasis

The evaluation of a patient with bronchiectasis entails elicitation

of a clinical history, chest imaging, and a workup to determine

the underlying etiology. Evaluation of focal bronchiectasis almost

always requires bronchoscopy to exclude airway obstruction by an

underlying mass or foreign body. A workup for diffuse bronchiectasis includes analysis for the major etiologies (Table 290-1), with

an initial focus on excluding CF. Pulmonary function testing is an

important component of a functional assessment of the patient.

TABLE 290-1 Major Etiologies of Bronchiectasis and Proposed Workup

PATTERN

OF LUNG

INVOLVEMENT

ETIOLOGY BY CATEGORY

(EXAMPLES) WORKUP

Focal Obstruction (aspirated foreign

body, tumor mass)

Chest imaging (chest

x-ray and/or chest CT);

bronchoscopy

Diffuse Infection (bacterial,

nontuberculous

mycobacterial)

Sputum Gram’s stain/

culture; stains/cultures for

acid-fast bacilli and fungi.

If no pathogen is identified,

consider bronchoscopy

with bronchoalveolar

lavage.

Immunodeficiency

(hypogammaglobulinemia,

HIV infection, bronchiolitis

obliterans after lung

transplantation)

Complete blood count with

differential; immunoglobulin

measurement; HIV testing

Genetic causes (cystic

fibrosis, Kartagener’s

syndrome, α1

 antitrypsin

deficiency)

Measurement of chloride

levels in sweat (for cystic

fibrosis), α1

 antitrypsin

levels; nasal or respiratory

tract brush/biopsy (for

dyskinetic/immotile cilia

syndrome); genetic testing

Autoimmune or rheumatologic

causes (rheumatoid arthritis,

Sjögren’s syndrome,

inflammatory bowel disease);

immune-mediated disease

(allergic bronchopulmonary

aspergillosis)

Clinical examination

with careful joint exam,

serologic testing (e.g.,

for rheumatoid factor).

Consider workup for

allergic bronchopulmonary

aspergillosis, especially

in patients with refractory

asthma.a

Recurrent aspiration Test of swallowing function

and general neuromuscular

strength

Miscellaneous (yellow

nail syndrome, traction

bronchiectasis from

postradiation fibrosis or

idiopathic pulmonary fibrosis)

Guided by clinical condition

Idiopathic Exclusion of other causes

a

Skin testing for Aspergillus reactivity; measurement of serum precipitins for

Aspergillus, serum IgE levels, serum eosinophils, etc.

In areas where tuberculosis is prevalent, bronchiectasis more

frequently occurs as a sequela of granulomatous infection. Focal

bronchiectasis can arise from extrinsic compression of the airway by

enlarged granulomatous lymph nodes and/or from development of

intrinsic obstruction as a result of erosion of a calcified lymph node

through the airway wall (e.g., broncholithiasis). Especially in reactivated tuberculosis, parenchymal destruction from infection can result

in areas of more diffuse bronchiectasis. Apart from cases associated

with tuberculosis, an increased incidence of non-CF bronchiectasis

with an unclear underlying mechanism has been reported as a significant problem in developing nations. It has been suggested that the high

incidence of malnutrition in certain areas may predispose to immune

dysfunction and development of bronchiectasis.

■ PATHOGENESIS AND PATHOLOGY

The most widely cited mechanism of infectious bronchiectasis is the

“vicious cycle hypothesis,” in which susceptibility to infection and poor

mucociliary clearance result in microbial colonization of the bronchial

tree. Some organisms, such as Pseudomonas aeruginosa, exhibit a particular propensity for colonizing damaged airways and evading host

defense mechanisms. Impaired mucociliary clearance can result from

inherited conditions such as CF or dyskinetic cilia syndrome, and it has

been proposed that a single severe infection (e.g., pneumonia caused

by Bordetella pertussis or Mycoplasma pneumoniae) can result in