# 17.12 Persistent problems and recovery after criti

# 17.12 Persistent problems and recovery after critical illness 3925 Mark E. Mikkelsen and Theodore J. Iwashyna

ESSENTIALS
Post-​intensive care syndrome is defined as new or worsening impair-
ment in cognition, mental health, or physical function that persists 
after a critical illness. The complexities of post-​intensive care syn-
drome come from the interactions of the patient’s premorbid mental 
health and physical function, the acute physiologic derangements 
and acute organ injury of the critical illness, and the side effects of 
procedures, treatments, and potential complications incurred during 
the critical illness. Problems are better described as challenging 
syndromes rather than specific actionable diagnoses, with the four 
major functional problems for patients being weakness, cognitive 
impairment, psychological problems, and new or worsened organ 
dysfunction. The sequelae of critical illness often extend beyond pa-
tients and impact the families of critically ill patients.
The clinical approach to post-​intensive care syndrome includes 
preventive strategies during the critical illness and a standardized ap-
proach to patients recovering from critical illness. Clinicians should 
be encouraged to engage the family in care and decision-​making to 
mitigate the risk of psychological distress for the patient and family. 
The intensive care unit diary is an established means to reduce psy-
chological distress in survivors and family members. Repeated and 
ongoing physical therapy may serve to both prevent deconditioning 
and to develop compensatory strategies for weakness that may have 
developed.
Post-​intensive care syndrome (PICS)
Most patients cared for in intensive care units (ICUs) survive that 
hospitalization. As a result an increasing number of patients are 
surviving critical illness but suffering a constellation of problems 
previously unrecognized or uncommon in general medical care. 
While many survivors will flourish after a critical illness, many ex-
perience neuropsychological and physical function impairments 
that impact their long-​term health, ability to return to work, and 
quality of life. The residual health effects of critical illness have been 
termed post-​intensive care syndrome (PICS).
Definition and conceptual overview
Post-​intensive care syndrome is defined as new or worsening im-
pairment in cognition, mental health, or physical function that 
persists after a critical illness. Memory and executive function are 
the cognitive domains most likely to be impaired; anxiety, depres-
sion, and post-​traumatic stress disorder are common psychiatric 
symptoms. ICU-​acquired weakness, also common after critical 
illness, can be due to myopathy, neuropathy, or a combination of 
the two, termed critical-​illness neuromyopathy. At the same time, 
it is also common for patients surviving critical illness to have 
exacerbations of previously well-​controlled chronic illnesses, or 
new conditions that were either not present or not previously 
diagnosed.
The complexities of post-​intensive care syndrome come from the 
interactions of the following (Fig. 17.12.1):
•	 The patient’s premorbid mental health and physical function
•	 The acute physiologic derangements and acute organ injury of the 
critical illness
•	 The side effects of procedures, treatments, and potential complica-
tions incurred during the critical illness
These lead to four major functional problems: weakness, cognitive 
impairment, psychological problems, and new or worsened organ 
dysfunction. These functional problems can lead to disability, in-
ability to return to social roles or prior employment, high recurring 
healthcare needs, and substantial burdens on caregivers, culmin-
ating in an increased risk of death that may persist for years after the 
apparent resolution of critical illness.
Epidemiology and specific manifestations
The risk factors associated with these impairments are multiple, 
complex, and (at present) incompletely understood. Factors thought 
to contribute include critical illness-​associated inflammation and 
ischaemia, hypotension, hypoxaemia, and hypoglycaemia, and con-
sequences of the acute illness and treatments received (e.g. immobil-
ization and delirium due, in part, to the use of sedative medications 
and mechanical ventilation) (Fig. 17.12.1).
17.12
Persistent problems and recovery 
after critical illness
Mark E. Mikkelsen and Theodore J. Iwashyna


Section 17  Critical care medicine
3926
While some acute intensive care unit experiences are associated 
with an increased prevalence of subsequent problems, causal rela-
tionships have not been proven. For example, the presence of de-
lirium, a common development in the ICU, does not predict poor 
long-​term outcomes with sufficient accuracy for prognostication 
in individual patients although there is a strong association at the 
population level. Equally true, the absence of specific problems in 
the ICU or immediately afterwards does not exclude the possibility 
of a patient experiencing post-​ICU sequelae.
The frequency of reported cognitive, mental health, and func-
tional impairments vary by study population and by the timing of 
assessments in relation to intensive care unit and hospital discharge 
(Table 17.12.1). At three months, 40% of survivors of shock or re-
spiratory failure have cognitive impairment consistent with that 
present in patients three months after moderate traumatic brain 
injury, 37% experience symptoms of mild depression or worse, 
and 32% have disabilities that limit basic activities of daily living. 
Symptoms of anxiety and post-​traumatic stress disorder after critical 
illness are similarly common.
While the definition of post-​intensive care syndrome focuses 
on neuropsychological and physical function, the effects of a crit-
ical illness extend beyond these domains. Sexual dysfunction, nu-
tritional deficiencies, loss of muscle mass, joint contractures, and 
scarring all occur after critical illness. Collectively, these changes 
contribute to the lower quality of life observed in survivors of crit-
ical illness.
Impairments in these domains frequently coexist, and im-
pairment in one domain can exacerbate impairment in another 
Fig. 17.12.1  Interactions in the critically ill patient leading to adverse long-​term outcomes. Pathways to functional 
impairments and disability are hypothesized but not yet fully described.
Inspired by Creditor, M. C. (1993). ‘Hazards of hospitalization of the elderly.’ Ann Intern Med, 118(3): 219–​223.
Table 17.12.1  The relationship between morbidity after critical illness and timing of assessments
ICU discharge
Hospital discharge
3 months
post-​discharge
12 months
post-​discharge
Cognitive Impairment
84%
46–​64%
40%
34%
Anxiety
24%
Depression
37%
28–​33%
Post-​traumatic stress disorder
22%
Functional impairment (activities of daily living)
32%
27%
Contracture, functionally significant
34%
23%
Sexual dysfunction
44%


17.12  Persistent problems and recovery
3927
(e.g. cognitive impairment may undermine coping strategies 
and exacerbate pre-​existing or new psychiatric disorders) or re-
sult in new impairment (e.g. post-​discharge depression predicts 
incident physical impairment).
PICS-​Family
Unfortunately, the sequelae of critical illness often extend beyond pa-
tients and impact the families of critically ill patients. Termed ‘PICS-​
Family’ (PICS-​F), family members of both surviving and deceased 
critically ill patients frequently experience psychological distress, 
including anxiety, depression, complicated grief, and post-​traumatic 
stress disorder, in addition to sleep disorders and panic attacks. As 
a result, family members may experience a reduced quality of life 
and reduced ability to care for and support the recovering patients. 
Risk factors associated with psychological distress include suffering 
the loss of a loved one, playing an active role as a surrogate decision-​
maker, ineffective communication from medical and nursing staff 
during the acute episode, and avoidant coping strategies during the 
acute events and afterwards. These effects can endure for months 
or years.
Recovery after critical illness
Post-​intensive care syndrome is a useful construct to conceptualize 
the impairments that survivors of critical illness may experience, yet 
it is incomplete as a guide to caring for individual patients. In par-
ticular, the concept of PICS may emphasize new problems caused 
by the critical illness. Yet, whether impairment is attributable to 
critical illness or not is less important than the degree and duration 
of impairment experienced by the patient. Further, patients often 
do not experience post-​intensive care syndrome as a fixed burden. 
Instead, it is a dynamic process of physiologic repair, ongoing med-
ical needs, personal rehabilitation efforts, and psychological, social, 
and pragmatic adaptation to these changes. Current evidence sug-
gests that this process is most dynamic during the first 3–​6 months 
after critical illness, although problems may persist for years. This is 
especially true if intercurrent illnesses stall recovery or precipitate 
further decline.
In the 90  days following critical illness, survivors are com-
monly re-​admitted to hospital. As many as one in four of these re-​
admissions require intensive care unit admission. Patients who have 
survived sepsis appear to be a particularly vulnerable population at 
high-​risk for re-​admission to hospital. Two observations have been 
made about these hospital re-​admissions. First, while many hos-
pital re-​admissions are for new or recrudescent infections, a large 
number (either a substantial minority or clear majority, depending 
on the study) are for problems that do not appear immediately re-
lated to the cause of the patient’s initial intensive care unit stay. 
Second, many hospital re-​admissions are for problems which, if an-
ticipated, may be averted by appropriate primary care in the early 
post-​hospitalization period; examples include congestive heart 
failure, acute renal failure, and aspiration pneumonitis.
Clinical approach
The clinical approach to post-​intensive care syndrome includes pre-
ventive strategies during the critical illness and a standardized ap-
proach to patients recovering from critical illness.
Whether encountering a patient after critical illness in an acute 
care hospital, a post-​acute care facility, or in the outpatient setting, 
a standardized approach should be used to examine the patient’s 
experiences and assess functional impairments. At present, there 
are few proven therapies for specific post-​ICU syndromes. Instead, 
practitioners should focus on recognizing conditions that exist and 
applying good clinical practice developed outside of the post-​ICU 
setting. There are some strategies that can be recommended as pre-
ventive strategies, and others that use a targeted diagnostic approach 
to patients with potential post-​intensive care syndrome complaints.
Preventive strategies
Strategies to prevent the development of post-​intensive care syndrome 
should begin in the intensive care unit. Evidence-​based strategies to 
decrease the duration of mechanical ventilation and ICU length of 
stay, duration of delirium, and increase functional independence are 
incorporated in the ‘ABCDE’ Bundle. The ABCDE bundle includes 
strategies to coordinate sedation and ventilator practices to achieve 
earlier liberation from mechanical ventilation, delirium assessment 
and management, and early ambulation to promote physical recovery.
The ICU Diary, a detailed account of events that occur in the ICU 
which are documented by both staff and family, is a strategy begun in 
the ICU and reviewed with the patient and family as an outpatient. 
It is an established means to reduce psychological distress in sur-
vivors and family members who may have limited or confused recall 
of events during the ICU stay. In conjunction with the review of the 
ICU Diary as an outpatient, clinicians should take the time to educate 
patients and caregivers about post-​intensive care syndrome as they 
assess the patient and caregivers for symptoms consistent with this 
syndrome.
To mitigate the risk of psychological distress for the patient and 
family, clinicians should engage the family in care and decision-​
making in the ICU and thereafter. Early and effective communica-
tion, within the first 48–​72 hours of the ICU stay, is recommended, 
in partnership with open visitation policies and the use of patient-​ 
and family-​centred ward rounds.
Priorities following discharge include assessment for post-​intensive 
care syndrome, coupled with education to provide patients and care-
givers with relevant information. There is currently active research 
on several possible strategies to facilitate recovery and prevent post-​
intensive care syndrome. Repeated and ongoing physical therapy has 
strong face validity and plausibility, and may serve to both prevent 
deconditioning and—​as in the pulmonary rehabilitation model used 
in COPD—​to develop compensatory strategies for weakness that may 
have developed. Several groups are exploring whether psychological 
or cognitive rehabilitation strategies are beneficial, but the effective-
ness of these strategies has not yet been proven. Early and intensive 
primary care access and close monitoring might be of benefit to accel-
erate recovery and prevent recurrent illness. Finally, there is growing 
interest in (but little evaluation of) the role of peer support groups for 
patients and families in improving recovery.
In some cases, this preventive care will be delivered in post-​ICU 
follow-​up clinics. Post-​ICU follow-​up clinics are an established prac-
tice in the United Kingdom and an emerging option within the United 
States, especially after stroke, trauma, or neonatal care. Yet, there is 
currently no consensus on their effectiveness or optimal structure.


Section 17  Critical care medicine
3928
Medication reconciliation after the ICU
While there is nothing specific to medication reconciliation after in-
tensive care unit treatment, it is clear that many medications are in-
appropriately stopped and started there. Population-​based research 
in Ontario suggested that HMG-​CoA reductase inhibitors (statins), 
antiplatelet agents, anticoagulants, and thyroxine were frequently 
discontinued inappropriately after hospital admissions that included 
an ICU stay. Conversely, medications that may be reasonable for 
short-​term treatment in the intensive care unit may be inappropri-
ately continued after discharge; attention to the potential effects of 
medications on cognitive health is warranted. Offenders in one or 
both of these categories may include antipsychotics (used to prevent 
or treat delirium in the ICU), short-​acting antihypertensives (used 
during transient hypertensive urgencies), proton pump inhibitors 
(used for stress ulcer prophylaxis), opioids and benzodiazepines 
(used for procedural pain, sedation, or unclear indications in the 
ICU). Clinicians should be aware that, due to insomnia and psychi-
atric symptoms, psychiatric medications are prescribed in up to 20% 
of patients in the year after a critical illness; the appropriateness of 
this is unclear. Colourful stories are often told of patients who resume 
taking one full set of medications they were prescribed before the in-
tensive care unit, and an entire second set of medications with which 
they were discharged: many duplicative, some unnecessary, others 
contraindicated.
Diagnostic approach
A comprehensive clinical evaluation after ICU treatment should re-
view the details of the recent critical illness and intervening events, 
including locations of care post-​discharge, in addition to conducting 
a physical examination. Based on the unique challenges faced by 
survivors of critical illness and the prevalence of neuropsychological 
and physical impairments, additional elements of the history and 
physical examination should be included as an initial screening 
strategy (see Table 17.12.2). A structured approach that ties together 
a health narrative precritical illness to the present state post-​critical 
illness can be used to identify new and unmasked health needs
Clinical investigations
Neuropsychological assessment
Because informal assessments of neuropsychological problems 
are known to have low sensitivity, survivors of critical illness 
should be screened for cognitive impairment and mental health 
disorders, including depression, anxiety, and post-​traumatic 
stress disorder. Several simple, validated screening tests are avail-
able for use (Table 17.12.3). Formal neuropsychological assess-
ment by a trained neuropsychologist may be useful to further 
characterize the type and severity of impairment in those who 
screen positive or are experiencing symptoms. The effectiveness 
of neurocognitive rehabilitation has not been fully studied after 
critical illness. However, given its utility in other disease states 
(e.g. traumatic brain injury), early referral to an interested prac-
titioner is reasonable. Those identified to have significant psy-
chiatric symptoms should be considered for referral to a mental 
health expert, in addition to consideration of prescribing psychi-
atric medications.
Functional assessment
Assessment of activities of daily living should be performed to 
assess for functional disability, which may guide referral to phys-
ical or occupational therapists to develop compensatory strat-
egies or assistive devices. In addition, the ‘Timed Get Up and 
Go’ test in which the patient is asked to stand up from a seated 
position, walk 3 metres, and return back to the seated position is 
a simple test to assess for functional status problems patients may 
not self-​report.
Lung function
In survivors who experienced acute respiratory failure, and acute 
respiratory distress syndrome (ARDS) in particular, lung function 
Table 17.12.2  A targeted approach to the history and physical 
examination after critical illness, accounting for health pre-​ and 
post-​critical illness
Critical illness history
Physical examination
Acute event
Complications, including detailed review of acute 
infections during the hospitalization
Focused assessment for:
Mobility
Joint contractures
Body composition
Post-​procedural scars
Medication reconciliation, including antibiotics, 
psychiatric prescriptions, and sleeping aid prescriptions
Post-​illness review of symptoms, including 
constitutional (fatigue, weight change, pain), 
cognition (memory, ability to think clearly), 
anxiety, depression, post-​traumatic stress disorder, 
insomnia, sensory changes (hearing, taste, 
vision), cardiopulmonary (dyspnoea, cough), 
musculoskeletal changes (loss of strength, mobility)
Dependent on screening, post-​illness functional 
assessment, including neuropsychological 
assessment, physical function, lung function, sexual 
function, nutritional, and sleep hygiene assessment
Recovery history post-​discharge, including locations 
of care and present support structure
Table 17.12.3  Suggested strategies for assessments post-​critical 
illness
Domain 
assessment
Instrument
Cognitive function
Modified Mini-​Mental State
Montreal Cognitive Assessment
Mental health
Hospital Anxiety and Depression Scale
Post-​traumatic stress syndrome 10-​questions 
inventory (PTSS-​10)
Functional 
assessment
Activities of daily living
Instrumental activities of daily living
Timed Get Up and Go Testa
Lung function
Pulmonary function tests, in those with symptoms or 
clinical history suggestive of lung dysfunction
Ancillary tests 
(imaging, laboratory 
testing)
Neither routine imaging or laboratory testing are 
recommended in general; assessments for those 
recovering from an infection are recommended to 
ensure resolution and for secondary prevention
a In this test, patients are asked to stand up from a seated position, walk 3 metres, and 
return back to the seated position. A normal time to accomplish the task is 10 seconds or 
less in healthy elders and longer times are associated with increased fall risk.


17.12  Persistent problems and recovery
3929
may be impaired after critical illness, although it is normalized sur-
prisingly often. Symptom-​directed testing is appropriate.
Imaging
Routine imaging after critical illness is not recommended. Rather, 
ancillary testing, including more advanced imaging such as com-
puted tomography or magnetic resonance imaging, should be re-
served for those with clinical symptoms and signs and based on 
established, routine health screening recommendations.
Ancillary tests
There is no formal recommendation to obtain specific labora-
tory testing after critical illness. Rather, laboratory testing should 
be obtained based on routine health maintenance and screening 
recommendations. In general, clinicians should be aware that an-
aemia is common after critical illness and testing should be reserved 
to examine resolution of acute organ dysfunction or as needed for 
safety monitoring.
Early treatment to avoid re-​admission to hospital
As noted above, re-​admission to hospital for infection as well as 
other ambulatory-​care sensitive conditions is common in the 90-​
days after discharge, and it may be beneficial to ensure rapid access 
and lower treatment thresholds for such conditions.
Compensation and rehabilitation strategies 
for identified problems
Clinicians should prioritize timely referral to ancillary services 
based on the patient’s symptoms and testing. While the benefits of 
strategies to improve outcome of post-​intensive care syndrome have 
not been proven, experts in cognitive and functional impairments 
can provide strategies to compensate for these impairments. While 
no post-​intensive care syndrome-​specific therapies yet exist, pru-
dent generalization from experience with other conditions may pro-
vide symptomatic relief and improved function. Further, in terms 
of health trajectory, vigilance is required to ensure that acute condi-
tions resolve and new symptoms and conditions are identified and 
managed in a timely and effective manner.
Given the complexity of care after critical illness, communica-
tion among care providers is of the utmost importance to help the 
patient navigate their post-​critical illness course. While the most 
effective strategy remains unclear, identifying an accessible point-​
person to oversee the coordination of care required after critical 
illness should be a priority. The number of services and related clin-
icians that may needed in the care of patients after critical illness 
can be substantial (see Table 17.12.4). As a result, communication 
and coordination from hospital discharge to the outpatient setting 
is essential. As many survivors of critical illness will be disabled, 
there are plausible benefits to engaging the patient’s support net-
work (family and friends) in the process. At the centre of these 
communications lies the patient, and while the focus shifts towards 
rehabilitation and recovery in many, palliative and hospice care 
may be reasonable considerations for others based on their symp-
toms and care preferences.
Conclusion
The success of critical care medicine in preventing death has led to 
substantial new challenges for clinicians throughout the healthcare 
system. Patient who might once have died in the intensive care unit 
or subsequently in hospital are surviving, often (but not always) 
with enduring problems—​and problems better described as chal-
lenging syndromes rather than specific actionable diagnoses. New 
approaches to diagnosis, classification, treatment, and symptom 
management are emerging, offering more hope for affected patients.
FURTHER READING
Davidson JE, Jones C, Bienvenu J (2012). Family response to critical 
illness: postintensive care syndrome-​family. Crit Care Med, 40, 618–​24.
Garrouste-​Orgeas M, et al. (2012). Impact of an intensive care unit 
diary on psychological distress in patients and relatives. Crit Care 
Med, 40, 2033–​40.
Hua M, et al. (2015). Early and late unplanned hospital readmissions 
for survivors of critical illness. Crit Care Med, 43, 430–​8.
Iwashyna TJ, et al. (2010). Long-​term cognitive impairment and func-
tional disability among survivors of severe sepsis. JAMA, 304, 1787–​94.
Mehlhorn J, et al. (2014). Rehabilitation interventions for postintensive 
care syndrome: a systematic review. Crit Care Med, 42, 1263–​71.
Needham DM, et al. (2012). Improving long-​term outcomes after dis-
charge from intensive care unit: report from a stakeholders’ confer-
ence. Crit Care Med, 40, 502–​9.
Pandharipande P, et al. (2010). Liberation and animation for ventilated 
ICU patients: the ABCDE bundle for the back-​end of critical care. 
Crit Care, 14, 157.
Pandharipande PP, et al. (2013). Long-​term cognitive impairment after 
critical illness. N Engl J Med, 369, 1306–​16.
Prescott HC, Angus DC (2018). Enhancing recovery from sepsis: a re-
view. JAMA, 319, 62–75.
Prescott HC, Langa KM, Iwashyna TJ (2015). Readmission diagnoses 
after hospitalization for severe sepsis and other acute medical condi-
tions. JAMA, 313, 1055–7.
Table 17.12.4  Potential services and expertise required in the care 
of the recovering critically ill patient
Acute care
Post-​acute care
Outpatient
Physical and 
occupational therapy
Acute rehabilitation
Physical and occupational 
therapy
Nutrition consultation
Home with home  
health services
Nutrition consultation
Respiratory therapy
Skilled care facility
Mental health services, 
including grief counselling 
for family members
Case manager to 
facilitate post-​acute 
care needs
Long-​term acute care 
hospital
Neuropsychology 
consultation
Palliative care for 
symptom management
Hospice care
Palliative care for 
symptom management 
and/​or hospice care
Surgery consultations
Support groups




SECTION 18
Respiratory disorders
Section editor: Pallav L. Shah
	18.1	 Structure and function  3933
18.1.1	 The upper respiratory tract  3933
Pallav L. Shah, J.R. Stradling, and S.E. Craig
18.1.2	 Airways and alveoli  3937
Peter D. Wagner and Pallav L. Shah
	18.2	 The clinical presentation of respiratory 
disease  3947
Samuel Kemp and Julian Hopkin
	18.3	 Clinical investigation of respiratory  
disorders  3956
18.3.1	 Respiratory function tests  3956
G. J. Gibson
18.3.2	 Thoracic imaging  3970
Susan J. Copley and David M. Hansell
18.3.3	 Bronchoscopy, thoracoscopy,  
and tissue biopsy  3992
Pallav L. Shah
	18.4	 Respiratory infection  4004
18.4.1	 Upper respiratory tract infections  4004
P. Little
18.4.2	 Pneumonia in the normal host  4008
Wei Shen Lim
18.4.3	 Nosocomial pneumonia  4022
Wei Shen Lim
18.4.4	 Mycobacteria  4026
Hannah Jarvis and Onn Min Kon
18.4.5	 Pulmonary complications of HIV infection  4031
Julia Choy and Anton Pozniak
	18.5	 The upper respiratory tract  4040
18.5.1	 Upper airway obstruction  4040
James H. Hull and Matthew Hind
18.5.2	 Sleep-​related breathing disorders  4048
Mary J. Morrell, Julia Kelly, Alison McMillan,  
and Matthew Hind
	18.6	 Allergic rhinitis  4059
Stephen R. Durham and Hesham A. Saleh
	 18.7	 Asthma  4067
Alexandra Nanzer-​Kelly, Paul Cullinan,  
and Andrew Menzies-​Gow
	 18.8	 Chronic obstructive pulmonary disease  4098
Nicholas S. Hopkinson
	 18.9	 Bronchiectasis  4142
R. Wilson and D. Bilton
	18.10	 Cystic fibrosis  4151
Andrew Bush and Caroline Elston
	18.11	 Diffuse parenchymal lung diseases  4166
18.11.1	 Diffuse parenchymal lung disease:  
An introduction  4166
F. Teo and A.U. Wells
18.11.2	 Idiopathic pulmonary fibrosis  4177
P.L. Molyneaux, A.G. Nicholson, N. Hirani,  
and A.U. Wells
18.11.3	 Bronchiolitis obliterans and cryptogenic 
organizing pneumonia  4185
Vasilis Kouranos and A.U. Wells
18.11.4	 The lung in autoimmune rheumatic 
disorders  4191
M.A. Kokosi and A.U. Wells
18.11.5	 The lung in vasculitis  4200
G.A. Margaritopoulos and A.U. Wells
	18.12	 Sarcoidosis  4208
Robert P. Baughman and Elyse E. Lower
	18.13	 Pneumoconioses  4219
P.T. Reid
	18.14	 Miscellaneous conditions  4235
18.14.1	 Diffuse alveolar haemorrhage  4235
S. J. Bourke and G.P. Spickett
18.14.2	 Eosinophilic pneumonia  4238
S. J. Bourke and G.P. Spickett
18.14.3	 Lymphocytic infiltrations of the lung  4241
S. J. Bourke


18.14.4	 Hypersensitivity pneumonitis  4244
S. J. Bourke and G.P. Spickett
18.14.5	 Pulmonary Langerhans’ cell 
histiocytosis  4256
S. J. Bourke
18.14.6	 Lymphangioleiomyomatosis  4257
S. J. Bourke
18.14.7	 Pulmonary alveolar proteinosis  4259
S. J. Bourke
18.14.8	 Pulmonary amyloidosis  4261
S. J. Bourke
18.14.9	 Lipoid (lipid) pneumonia  4263
S. J. Bourke
18.14.10	 Pulmonary alveolar microlithiasis  4265
S. J. Bourke
18.14.11	 Toxic gases and aerosols  4267
Chris Stenton
18.14.12	 Radiation pneumonitis  4271
S. J. Bourke
18.14.13	 Drug-​induced lung disease  4272
S. J. Bourke
	18.15	 Chronic respiratory failure  4282
Michael I. Polkey and P.M.A. Calverley
	18.16	 Lung transplantation  4292
P. Hopkins and A. J. Fisher
	18.17	 Pleural diseases  4305
D. de Fonseka, Y.C. Gary Lee, and N.A. Maskell
	18.18	 Disorders of the thoracic cage and 
diaphragm  4328
John M. Shneerson and Michael I. Polkey
	18.19	 Malignant diseases  4338
18.19.1	 Lung cancer  4338
S.G. Spiro and N. Navani
18.19.2	 Pulmonary metastases  4360
S.G. Spiro
18.19.3	 Pleural tumours  4361
Y.C. Gary Lee
18.19.4	 Mediastinal tumours and cysts  4368
Y.C. Gary Lee and Helen E. Davies
Section 18  Respiratory disorders