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