ATELECTASIS 215
McFadden E (2003) Acute severe asthma. American Journal of
Respiratory and Critical Care Medicine 168: 740759.
National Asthma Education and Prevention Program Expert Panel
Report: guidelines for the diagnosis and management of asthma,
Update on Selected Topics 2002. Journal of Allergy and clin-
ical Immunology 110(5 pt 2): S141S219.
NHLBI/WHO (2004) Global initiative for asthma: global strategy
for asthma management and prevention. NHLBI/WHO Work-
shop Report NIH 02-3659. Bethesda: NIH.
ATELECTASIS
P A Kritek, Brigham and Womens Hospital at Harvard
Medical School, Boston, MA, USA
& 2006 Elsevier Ltd. All rights reserved.
Abstract
Atelectasis is the loss of volume resulting from decreased gas in
a given portion of lung. The mechanisms that cause atelectasis
can be divided into three categories: passive, adhesive, and re-
sorptive. Passive atelectasis results from space-occupying lesions
in either the pleural space or the parenchyma compressing ad-
jacent normal lung tissue. Adhesive atelectasis is caused by a
decrease in the level or activity of surfactant leading to an in-
crease in surface tension in the alveolus and subsequent col-
lapse. Resorptive atelectasis ensues when there is partial or
complete occlusion of flow of gas between alveoli and the tra-
chea. Oxygen, carbon dioxide, and nitrogen will diffuse from
the alveolus into the capillary until all gas is removed from the
alveolar space. Small areas of atelectasis can be found in normal
lungs due to the effects of gravity. Pneumothoraces or large
bullae can result in passive atelectasis. Adhesive atelectasis is a
feature of respiratory distress syndrome of the neonate as well
as acute respiratory distress syndrome in adults. Resorptive ate-
lectasis is found distal to an obstructive lesion, such as a tumor
or mucus plug. Atelectasis associated with anesthesia is complex
and caused by a combination of these mechanisms.
Description
Atelectasis is the loss of volume resulting from de-
creased gas in a given portion of lung. These changes
can be small, affecting only subsegmental regions, or
more dramatic, leading to collapse of an entire lung.
The mechanisms that result in atelectasis can be di-
vided into three categories: passive, adhesive, and re-
sorptive. Each of these is discussed individually. Note
that although discussions of radiographic descriptions
of atelectasis are included, the discussion is grounded
in these pathophysiologic aspects of atelectasis.
Passive Atelectasis
Passive atelectasis results from a space-occupying le-
sion within the pleural space or the parenchyma
OByrne PM and Thomson NC (eds.) (2001) Manual of Asthma
Management, 2nd edn. London: W B Saunders.
Rodrigo G, Rodrigo M, and Jesse B (2004) Acute asthma in adults:
a review. Chest 125(3): 10811102.
Tattersfield A, Knox A, Britton J, and Hall I (2002) Asthma. Lan-
cet 360: 13131322.
Thomson NC, Chaudhuri R, and Livingston E (2004) Asthma
and cigarette smoking. European Respiratory Journal 24:
822833.
thereby creating a smaller space in which to maintain
the inflated lung (Figure 1). As a result, adjacent lung
tissue will lose gas and subsequently collapse. This
form of atelectasis is referred to as passive because the
collapsed lung is not inherently abnormal but is being
affected by an adjacent pathologic process. If the in-
citing cause of the atelectasis is resolved (e.g., a
pneumothorax is evacuated), the underlying atelecta-
tic lung should reexpand and return to normal func-
tion. It should be noted, however, that after a segment
of lung has collapsed, there are local changes in per-
meability, inflammatory markers, alveolar macro-
phage function, and surfactant associated with all
types of atelectasis that may predispose to abnormal
function upon reinflation.
Adhesive Atelectasis
Adhesive atelectasis results from the absence, loss, or
decreased activity of surfactant within the alveoli
(Figure 2). Surfactant, produced by type II alveolar
cells, decreases surface tension as alveolar surface
area decreases and balances the retraction forces of
the lung in order to avoid end-expiratory alveolar
collapse. When surfactant is decreased or inacti-
vated, the balance is upset and atelectasis ensues. In
this situation, there is loss of gas volume based on
mechanical forces within the alveolus as opposed to
external compression.
This form of atelectasis can occur in the neonatal
infant in the setting of immature type II alveolar cells
and decreased surfactant production. Alternatively,
certain adult disease states, including ventilator-as-
sociated pneumonia and acute respiratory distress
syndrome (ARDS), are associated with decreases in
absolute surfactant levels or its activity.
Resorptive Atelectasis
Resorptive atelectasis results when there is partial or
complete occlusion of flow of gas between alveoli
216 ATELECTASIS
Pleural space
Normal alveolus
Figure 1 Normal alveolus and passive atelectasis.
Normal alveolus
Figure 2 Normal alveolus and adhesive atelectasis.
and the trachea (Figure 3). As the section of ob-
structed lung continues to be perfused, the partial
pressure of oxygen in the alveolus equilibrates with
that in the alveolar capillary. The loss of oxygen in
the alveolus leads to increased concentrations of ni-
trogen and carbon dioxide in the alveolus, and sub-
sequent gradients result in movement of both gases
from the alveolus into the capillary. This process will
continue until all gas has been removed from the
airspace, a phenomenon that takes 1824 h in nor-
mal volunteers with a completely occluded lobe.
Resorptive atelectasis can result from any cause of
obstruction to airflow. Common etiologies include
Pneumothorax
Passive atelectasis
Edema and
decreased
surfactant
Adhesive atelectasis
tumor, mucus plug, and foreign body. The process of
resorptive atelectasis is thought to occur more quickly
in the setting of oxygen-rich gas because the first step
of oxygen absorption is more rapid and there is a
larger portion of gas that is absorbed initially.
Atelectasis in Normal Lung Function
By definition, atelectasis is caused by loss of gas from
a normally gas-filled section of lung. However, there
is a form of passive atelectasis that is commonly seen
in normal lungs that is referred to as dependent
atelectasis. This is the loss of volume in alveoli and

Normal alveolus
Figure 3 Normal alveolus and resorptive atelectasis.
small airways in the lower lung zones based on grav-
ity-related decreases in transpulmonary pressures.
Although these areas of atelectasis may have physio-
logic consequences in patients with underlying lung
disease (e.g., ARDS), the small loss of volume most
likely has no physiologic consequence in normal sub-
jects. The increased use of computed tomography
(CT) has led to a greater awareness of these changes.
Dependent atelectasis will resolve with position
change, as demonstrated by repeated tomography
with the patient in the prone position.
Atelectasis in Respiratory Diseases
Passive Atelectasis
Passive atelectasis can occur in a generalized or lo-
calized manner. In the setting of a large pneumotho-
rax, the majority of the parenchyma of the ipsilateral
lung will undergo passive atelectasis. In contrast,
lung tissue adjacent to a bleb or a parenchymal cyst
can collapse in a more localized form of passive ate-
lectasis. Both examples illustrate a space-occupying
phenomenon that causes subsequent loss of gas and
collapse. With relief of a large space-occupying le-
sion, such as a pneumothorax, the underlying lung
may develop reexpansion pulmonary edema. This
process is thought to result from changes in pulmo-
nary capillary permeability but is not well under-
stood. The pulmonary edema is usually transient and
resolves with supportive care.
There is a unique form of passive atelectasis
termed rounded atelectasis. This description is
ATELECTASIS 217
Tumor
Resorptive atelectasis
reserved for collapse of lung associated with pleural
thickening, most commonly found in association
with asbestos exposure. The etiology of rounded
atelectasis is not well understood but is thought to
result from pleural fibrosis contracting and causing
adjacent lung to curl upon itself and collapse. The
radiographic findings are best characterized on chest
tomography. The lesions are classically peripheral,
subpleural, uniform in density, and mass-like in ap-
pearance. They often have a curvilinear opacity of
bronchi and vessels (termed a comet tail) extending
toward the hilum. Care needs to be taken in diag-
nosing a lung nodule as rounded atelectasis purely on
CT findings because there are many reports of ma-
lignancy masquerading as rounded atelectasis.
Adhesive Atelectasis
The classic example of absorptive atelectasis is that
of respiratory distress syndrome (RDS) of the neo-
nate. As discussed previously, type II alveolar cells
are often immature and not fully functional in the
preterm infant, predisposing the infant to RDS.
There have been significant decreases in morbidity
and mortality in RDS with the initiation of surfactant
(natural or synthetic) replacement in the immediate
neonatal period. This improvement is in part due to
the marked decrease in atelectasis and resulting im-
proved gas exchange with surfactant therapy.
Many studies demonstrate decreased surfactant
levels in adults with ARDS. There is also experi-
mental evidence for decreased surfactant activity in
the setting of leakage of plasma proteins into the al-
veolar space. At the same time, studies using CT have
218 ATELECTASIS
demonstrated areas of atelectasis in ARDS. The etio-
logy of this atelectasis is likely multifactorial. There
are increased changes in dependent lung zones sug-
gesting a component of passive atelectasis accompa-
nying the adhesive atelectasis, the latter presumably
from decreased quantity or activity of surfactant.
Some believe that the recurrent opening and clos-
ing of small, atelectatic lung units contributes to
ventilator-induced lung injury (termed atelectrau-
ma). In response to this, there has been increasing
research on how to avoid or overcome the atelectasis
associated with ARDS. Efforts to replace surfactant
through a variety of modalities have not demon-
strated a mortality benefit, although some studies
have shown improved gas exchange. Lung ventila-
tion strategies aimed at maintaining an open lung,
such as recruitment maneuvers, high-frequency jet
ventilation, and conventional ventilation with high
positive end expiratory pressure (PEEP), have shown
transient rises in oxygenation but no improvement
in mortality. There is no conclusive evidence sup-
porting any specific treatment of atelectasis associ-
ated with ARDS.
Resorptive Atelectasis
Endobronchial tumors are a common cause of re-
sorptive atelectasis, often resulting in segmental or
lobar collapse. One retrospective review reported an
incidence of atelectasis in one of five patients with
small cell lung cancer. Because these are gradual
processes occurring over weeks to months, the at-
electatic lung often does not completely reexpand
or function normally if the obstruction is relieved.
However, because there is a risk for postobstructive
pneumonitis and there is evidence for increased bac-
terial growth in atelectatic lung, clinicians will often
attempt to minimize the obstruction.
In contrast to the more gradual development of
atelectasis with tumor growth, resorptive atelectasis
can occur rapidly with acute occlusions of large air-
ways. Mucus plugs, in both patients with asthma and
those with altered secretion clearance, have been de-
scribed as causes of resorptive atelectasis. Resorptive
atelectasis has also been reported with malpositioned
endotracheal tubes that selectively intubate the right
lung. In a short period of time, the entire left lung can
undergo atelectasis that will resolve with reposition-
ing of the endotracheal tube.
Atelectasis Associated with General Anesthesia
Atelectasis associated with general anesthesia de-
serves special mention because it occurs at rates as
high as 90% of anesthetized patients (as detected
by CT) and is often clinically significant. Lobar
atelectasis can result in parenchymal shunt and be
manifest as marked hypoxemia. There is evidence of
a positive correlation between the amount of at-
electatic lung and the degree of hypoxemia.
The atelectasis associated with anesthesia is caused
by multiple mechanisms. The first contributor is
dependent atelectasis (a form of passive atelectasis)
from prolonged recumbent positioning with exag-
gerated effects of gravity. There is also evidence of
changes in diaphragm position and shape with supine
positioning for anesthesia contributing to dependent
atelectasis. These effects are more pronounced when
neuromuscular blockade is used in conjunction
with anesthesia. All these changes are especially pro-
nounced in morbidly obese patients. Some an-
esthesiologists advocate for intermittent use of large
tidal volume breaths to overcome atelectasis intra-
operatively, whereas others advocate for elevated
levels of PEEP with ventilation.
Administration of supplemental oxygen as part of
mechanical ventilation contributes to resorptive ate-
lectasis. Results are mixed with regard to whether
higher inspired fractions (80100%) during induc-
tion and maintenance of anesthesia increase the
likelihood of atelectasis compared to lower oxygen/
nitrogen mixtures. There is also evidence of early
airway closure during anesthesia contributing to the
resorptive mechanism of atelectasis. It has been sug-
gested that repeated episodes of atelectasis, from the
previously mentioned means, can also lead to im-
paired surfactant function resulting in a component
of adhesive atelectasis as well.
The issues of atelectasis often persist into the post-
operative period, resulting in persistent hypoxemia.
The resorptive atelectasis associated with higher in-
spired fractions of oxygen persists after extubation
despite attempts at recruitment at the end of the op-
eration. Dependent atelectasis, which in the normal
subject will resolve with changes in position and deep
breathing, often persists due to decreased mobility,
pain, and sedation in the postoperative period. These
conditions also commonly lead to impaired clearance
of secretions predisposing to obstruction of airways
and resorptive atelectasis. Deep breathing, incentive
spirometry, vibration beds, chest physiotherapy, non-
invasive ventilation, and therapeutic bronchoscopy
all seem to have similar results in terms of resolution
of postoperative atelectasis.
See also: Alveolar Surface Mechanics. Breathing:
Breathing in the Newborn. Diffusion of Gases. Lung
Imaging. Mucus. Oxygen Therapy. Peripheral Gas
Exchange. Physiotherapy. Signs of Respiratory

Disease: Lung Sounds. Surfactant: Overview. Venti-
lation, Mechanical: Positive Pressure Ventilation.
Further Reading
Brower RG, et al. (2003) Effects of recruitment maneuvers in pa-
tients with acute lung injury and acute respiratory distress syn-
drome ventilated with high positive end-expiratory pressure.
Critical Care Medicine 31(11): 25922597.
Fraser RS and Parae PD (1999) Fraser and Paraes Diagnosis of
Diseases of the Chest, 4th edn. Philadelphia: Saunders.
Gunther A, et al. (2001) Surfactant alteration and replacement in
acute respiratory distress syndrome. Respiration Research 2(6):
353364.
Hallman M, Glumoff V, and Ramet M (2001) Surfactant in res-
piratory distress syndrome and lung injury. Comparative Bio-
chemistry and Physiology Part A: Molecular & Integrative
Physiology 129(1): 287294.
Hedenstierna G and Rothen HU (2000) Atelectasis formation
during anesthesia: causes and measures to prevent it. Journal of
Clinical Monitoring and Computing 16(56): 329335.
AUTOANTIBODIES
O C Ioachimescu, Cleveland Clinic Foundation,
Cleveland, OH, USA
& 2006 Elsevier Ltd. All rights reserved.
Abstract
Autoimmunity represents an immune response directed against
self-antigens, which may be (artificially) separated into T-cell
and B-cell responses. The importance of the B cells in autoim-
munity is correlated to the production of several autoantibodies,
which have a role in diagnosis, pathogenesis, guiding therapy,
and predicting outcome of the patients with these conditions.
Among these autoantibodies, antineutrophil cytoplasm anti-
bodies (ANCAs) have been distinguished as very important in
several conditions, such as Wegeners granulomatosis, micro-
scopic polyangiitis, Goodpastures syndrome, drug-related vas-
culitides, etc. We review in this article the importance of
different classes of autoantibodies and their relationship to un-
derlying disorders.
Introduction: Autoimmunity and Lung
Disorders
The phenomenon of autoimmunity has been the ob-
ject of exploration for over a century. Recent tech-
nical and methodological advances in the study of
cellular and biochemical processes of autoimmunity
have led to a publication big bang. Nevertheless,
the etiopathogenesis of most autoimmune disorders
remains, to date, largely unknown. In this article, we
discuss the basic mechanisms leading to autoimmu-
nity, as we understand them today, and then the
AUTOANTIBODIES 219
Kreider ME and Lipson DA (2003) Bronchoscopy for atelectasis in
the ICU: a case report and review of the literature. Chest 124(1):
344350.
Magnusson L and Spahn DR (2003) New concepts of atelectasis
during general anaesthesia. British Journal of Anaesthesia 91(1):
6172.
Peroni DG and Boner AL (2000) Atelectasis: mechanisms, diag-
nosis and management. Paediatric Respiratory Reviews 1(3):
274278.
Rouby JJ, et al. (2003) Acute respiratory distress syndrome: les-
sons from computed tomography of the whole lung. Critical
Care Medicine 31(4 supplement): S285S295.
Spragg RG, et al. (2004) Effect of recombinant surfactant
protein C-based surfactant on the acute respiratory distress
syndrome. New England Journal of Medicine 351(9): 884
892.
Vaaler AK, et al. (1997) Obstructive atelectasis in patients with
small cell lung cancer. Incidence and response to treatment.
Chest 111(1): 115120.
Woodring JH and Reed JC (1996) Types and mechanisms of
pulmonary atelectasis. Journal of Thoracic Imaging 11(2):
92108.
relevance of several classes of autoantibodies in var-
ious lung conditions.
An autoimmune disorder is a pathologic condition
caused by an autoimmune response, which is critically
dependent upon antigen quality, concentration, and
persistence, and the magnitude of the interaction be-
tween self and foreign components. The autoimmune
response leads to end-organ organ-damage through
cellular or humoral mechanisms. The humoral re-
sponse is represented by antibody-mediated injury,
which could be differentiated in direct, cytotoxic an-
tibody damage or immune complex-related damage.
Despite their diverse etiology, there are several patho-
genetic mechanisms which are common to all auto-
immune conditions. With few exceptions, they require
the presence of self-reactive CD4 positive lymphocytes.
The immune system is naturally endowed with
myriad mechanisms responsible for recognition of
and defense against foreign assaults. Direct and rapid
responses can be mediated by a set of germline-en-
coded receptors, called Toll-like receptors (TLRs),
which recognize specifically the molecular determi-
nants of various pathogens. Activation of the innate
immune defense mechanisms leads to a response
from different cell types (local dentritic cells, natural
killer lymphocytes, neutrophils, monocytes, ma-
crophages, basophils, eosinophils, and mastocytes),
ranging from production of chemokines, cytokines,
adhesion molecules, antimicrobial, pro- and anti-
apoptoic factors. This response is reproducible (acts