WHAT'S NEW IN RESPIRATORY DISORDERS

Published with
Volume 32:5 2004

Whats new in ...

Respiratory disorders

Medicine

Martin F Muers

Recent developments in non-asthma respiratory disorders include

guidelines for and studies of the management of community-acquired
pneumonia, chronic obstructive pulmonary disease, obstructive sleep
apnoea and pneumothorax, changes in the classification of idiopathic
pulmonary fibrosis, and new techniques in surgery and imaging.
Community-acquired pneumonia (CAP)
New British Thoracic Society guidelines
for the management of CAP were published in 2001.1 There is an emphasis on
identifying patients with severe pneumonia at high risk of death, based on the
CURB criteria (Figure 1). Patients with
two or more criteria should be managed
for severe pneumonia in a specialist respiratory care unit where close monitoring
is available. This approach was recently
validated, with the addition of age over
65 years as an additional risk factor,2 and
is easier to use than the more complex
Pneumonia Severity Index developed in
1997.3 Other adverse prognostic features
include coexisting disease, hypoxaemia
(SaO2 < 92% or PaO2 < 8 kPa) regardless of FiO2, and bilateral or multi-lobe
involvement. These should be considered
particularly in patients with only one of
the core features. Microbiological investigations in all patients with severe CAP
should include blood culture, sputum for
microscopy, culture and sensitivity testing,
pneumococcal and Legionella antigen testing (urine sample) and paired serological
testing. Other additional investigations
may be necessary depending on individual
circumstances and clinical suspicions.

Choice of antibiotics depends on local recommendations based on known patterns

of resistance, which vary markedly.4 In the
UK, the recommendation for severe CAP
is an intravenous combination of a broadspectrum, -lactamase-stable antibiotic
(e.g co-amoxiclav) or a second-generation
or third-generation cephalosporin with a
macrolide (e.g. clarithromycin).1

Chronic obstructive pulmonary disease

(COPD)
Tiotropium is a new, long-acting anticholinergic bronchodilator with muscarinic
M(1) and M(3) receptor subtype selectivity. It dissociates more slowly from
M(3) receptors (which are located in the
bronchial epithelium), enabling once-daily
administration.5 Early studies have shown
that the drug is well tolerated, with a
safety profile similar to that of placebo.6,7
The full clinical benefits of tiotropium
take up to 8 days to develop and there is a
washout period of 72 hours. It should not
be used in conjunction with ipratropium
bromide. Compared with salmeterol8 and
ipratropium9, tiotropium improved dyspnoea, bronchodilatation and quality of
life. The new NICE evidence-based COPD
guidelines recommend use of a long-acting

Martin F Muers MA DPhil FRCP is Consultant Respiratory Physician in the Respiratory Unit at
Leeds General Infirmary, Leeds, UK.

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bronchodilator, either tiotropium, 18 g

once daily, or a long-acting -agonist, for
bronchodilator treatment in patients who
remain symptomatic after use of shortacting drugs.10

Non-invasive positive-pressure
ventilation (NIPPV)
A recent meta-analysis of NIPPV in patients with COPD has confirmed the benefits of this treatment.11 It recommends that
NIPPV should be the first-line intervention,
in addition to the usual medical care, in
the management of respiratory failure secondary to an acute exacerbation of COPD
in all suitable patients. NIPPV should be
tried early in respiratory failure, after about
1 hour of usual medical management, if the
patient remains acidotic (pH 7.257.35),
and to avoid endotracheal intubation and
reduce treatment failure.
Contraindications to NIPPV include
reduced consciousness level, severe hypoxaemia and the presence of copious
respiratory secretions.12

Sleep disorders
Obstructive sleep apnoea (OSA) is associated with an increased risk of cardiovascular disease and stroke. It is an independent risk factor for hypertension and
has been implicated in the pathogenesis
of congestive cardiac failure, pulmonary
hypertension, arrhythmias and atherosclerosis.13 The Sleep Heart Health Study
has demonstrated modest-to-moderate
effects of OSA on cardiovascular disease
within a range of apnoea/hypopnoea index

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WHAT'S NEW IN RESPIRATORY DISORDERS

CURB criteria for identification of patients with

severe pneumonia at high risk of death

C
U
R
B
65

New mental confusion (abbreviated mental test score 8)

Urea > 7 mmol/litre
Respiratory rate > 30/minute
Blood pressure systolic < 90 mm Hg and/or diastolic 60 mm Hg
Age > 65 years

(AHI) values that are considered normal or

only slightly elevated.14
A recent meta-analysis confirmed
that continuous positive airway pressure
(CPAP) therapy significantly improves
subjective and objective measures of
sleepiness in patients with OSA, and that
patients with more severe apnoea and
sleepiness derive most benefit. 15 This
is supported by a study suggesting that
patients with an AHI of more than 30 but
with no daytime sleepiness derive no benefit from CPAP in terms of quality of life,
attention, coordination and arterial blood
pressure.16 It is suggested that treatment
is therefore not indicated in non-sleepy
patients with a pathological AHI. Evidence
is lacking regarding long-term use of CPAP
in asymptomatic patients with a high AHI
to reduce cardiovascular risk.

Cryptogenic fibrosing alveolitis (CFA)

Typical patients with CFA present over the
age of 60 years with a relatively short history of increasing breathlessness, Velcro
crackles, finger clubbing and desaturation on exercise, and exhibit interstitial
shadowing at the lung bases. Further tests
reveal restrictive lung disease, and highresolution CT (HRCT) shows a combination
of ground glass (cellular infiltration of the
interstitium and/or the alveoli) and fibrosis
(usually subpleural) with honeycombing
and traction bronchiectasis.
It is recognized that CFA is usually
progressive, corticosteroids and other
immunosuppressive treatments are relatively ineffective, and the median survival
is poor (about 3 years). However, it is now
clear that CFA is not a single disease but
several (Figure 2), and these have different
prognoses.17,18
Usual interstitial pneumonia (UIP) is the
classical form, in which lung biopsy shows

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heterogeneous features within the same

field, areas of acute interstitial inflammation and cellular exudate, and other areas
of established fibrosis. It is this mixture
that defines the condition and is correlated
with a poor prognosis.
In desquamative interstitial pneumonia, macrophages fill the alveolar spaces.
Patients are more likely to be younger,
and more than 90% are smokers. HRCT
shows more ground-glass change and little
fibrosis. Management includes smoking
cessation, because tobacco is thought to be
causative.19 The response to corticosteroids
is relatively good.
Respiratory bronchiolitis interstitial lung
disease is an extension of the tobaccorelated inflammatory bronchiolitis that
is a usual feature of COPD. In these patients, the bronchiolitis is accompanied
by macrophage infiltration around the
respiratory bronchioles. Patchy groundglass changes are seen on HRCT. The interstitial lung disease is thought to be caused
by smoking, and management involves
smoking cessation and oral corticosteroids,
to which the response is good.
In nonspecific interstitial pneumonitis,
HRCT shows an unusual combination
of both ground-glass areas and patchy
consolidation. On biopsy, the histological

changes are uniform, as if the same process

is occurring in all lung areas at a uniform
rate. The heterogeneity of UIP is not seen.
The prognosis is relatively good (70%
5-year survival).
Management of UIP: in 1999, a preliminary randomized controlled trial (RCT)
showed that nine patients with UIP randomized to receive interferon-1b plus
prednisolone, 7.5 mg, fared better than
nine patients randomized to oral prednisolone alone at a dose of 7.550 mg per
day.20 Pulmonary function, arterial gases
and desaturation on exercise all improved
at 12 months, with no serious adverse
effects.
It is thought that interferon-1b acts by
reducing transcription of genes involved
in the production of transforming growth
factor 1 and connective tissue growth
factors. However, the results of a larger
RCT are now available and have shown
an unexpected and unacceptable risk of
abrupt deterioration. Thus, despite early
promise, interferon-1b is not currently
recommended or available for the treatment of this difficult disease.

Surgery for emphysema

Lung volume reduction surgery (LVRS):
medical therapy is of only limited benefit
in severely disabled patients with emphysema. As a result, there has been enthusiasm for excision of the most severely
affected areas of lung to achieve relief of
symptoms by restoration of pulmonary
mechanics.
After the initial report,21 a large RCT
has now been undertaken.22 Patients with
severe emphysema underwent pulmonary
rehabilitation and then were randomly
allocated to continued medical treatment
or LVRS. The results were as follows.

Classification of idiopathic interstitial pneumonia

Usual interstitial pneumonia (cryptogenic fibrosing alveolitis)

Respiratory bronchiolitis interstitial lung disease
Desquamative interstitial pneumonia
Acute interstitial pneumonia
Nonspecific interstitial pneumonia

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WHAT'S NEW IN RESPIRATORY DISORDERS

Surgery is contraindicated in patients

with a forced expiratory volume in
1 second of less than 20% predicted and
either homogeneous emphysema on CT or
a transfer factor of less than 20%.
Exercise capacity improved by more
than 10 W in only 16% of the patients in
the surgery group and 3% in the medical
group (p < 0.001).
Surgery offered no survival benefit
except in patients who had predominantly
upper lobe disease and were severely
breathless.
The surgery is expensive at about
$190,000 per quality-adjusted life-year
gained. This was reduced to $98,000 in
the subgroup of patients most likely to
benefit.
It is possible that LVRS could be offered
to patients with severe breathlessness and
predominantly upper lobe disease, but it
should continue to be part of multi-centre
studies.
Bronchoscopic lung volume reduction: there is interest in bronchoscopic
techniques in which stents with one-way
valves are placed endoscopically to deflate
emphysematous areas and reduce lung
volume non-surgically.23 These methods
are experimental, however, and their future
clinical impact is unknown.

Positron emission tomography (PET) in

the diagnosis and management of
lung cancer
Physicians often face dilemmas in the
diagnosis and management of solitary
pulmonary nodules or masses that appear
to be resectable tumours after history,
examination, radiography and CT. CT is
often thought to be entirely accurate, but its
sensitivity and specificity in this situation
is only about 6080%.
Some masses prove to be benign, but
CT cannot distinguish these.
Hilar and mediastinal nodes of more
than 1 cm diameter on CT are assumed
to be malignant, but some of those of less
than 1 cm are malignant, and some larger
nodes are benign.
Some metastases are clinically silent
and not visible on CT. Such patients are
not cured by thoracic surgery and relapse
shortly afterwards.
These inaccuracies partly explain why
5-year survival after surgery for lung cancer
is only about 40%.

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PET exploits the fact that cancer cells

take up glucose more avidly than benign
cells. Fluoro-182-deoxyglucose (FDG) is an
isotopically labelled glucose analogue containing positron (proton)-emitting fluorine.
Cancer cells lack the enzyme hexokinase,
which enables clearance of FDG from
normal cells; FDG therefore persists and
accumulates, emitting a signal that can be
scanned.
A meta-analysis showed that PET has a
sensitivity of 97% and a specificity of 78%
for pulmonary nodules of diameter down
to about 1 cm.24 PET is also superior to CT
for mediastinal nodes; weighted average
sensitivities were 84% and specificities
were 95% in an analysis of twelve studies.25
FDG accumulates naturally in brain tissue,
so PET cannot image cerebral metastases.
For other extrathoracic metastases (e.g.
liver, bone, adrenals), however, the sensitivity of PET is 93% and the specificity
88%.
PET has disadvantages of cost (about
800 per scan), and the fact that the isotope
has a relatively short half-life and needs a
cyclotron for generation. Nevertheless, it
has a potential to substantially improve the
accuracy of diagnosis and staging of lung
cancer before radical treatment,26 and will
probably emerge as a standard imaging
technique for this purpose in the next few
years.

Management of pneumothorax
National guidelines in the early 1990s
emphasized aspiration and the usefulness
of small chest drains (1014 F). Two new
major guidelines are now available.27,28 The
main points are as follows.
It is important to distinguish primary
from secondary pneumothorax. The latter
is caused by lung disease or trauma and
requires more active management, including admission for a minimum of 24 hours
after primary treatment.
A rim of air of less than 2 cm on the
inspiratory film (expiratory films are
not required) should be regarded as a
small pneumothorax. A rim larger than
this implies that more than 50% of the
hemithorax is filled with air; this is a large
pneumothorax.
Patients with a small primary pneumothorax who are not breathless can be discharged home with a follow-up radiograph
at 2 weeks and advice not to fly for at least
6 weeks after full resolution.

Initial management of all other patients

with primary pneumothorax should be
with aspiration.
Tube drainage with a 1014 F catheter
is indicated if aspiration of a primary
pneumothorax fails. An underwater seal
or a flutter valve is appropriate. Suction
should not be applied for 48 hours. Any
pneumothorax that does not resolve after
48 hours requires specialist referral, and
surgery is likely if there is no resolution at
5 days.
A tube should not normally be clamped
under any circumstances. The Seldinger
technique is likely to become standard,
but more experience is needed.
Intercostal drainage is required for all
those with a secondary pneumothorax,
except asymptomatic patients under the
age of 50 years with a small pneumothorax.
These pneumothoraces can be aspirated.
All patients admitted for observation
as primary management should receive
high-flow oxygen (e.g. 10 litres/minute
by mask), unless they have COPD. Air reabsorption is about 2% of the hemithorax
volume per 24 hours, and this is increased
fourfold by oxygen, which displaces nitrogen from the pleural space.
The lifetime risk of a smoker developing
a pneumothorax is 120 times greater than
that in non-smokers. Smoking cessation
should be part of the management of all
such cases.
Indications for surgery are a second
ipsilateral pneumothorax, a contralateral
pneumothorax, bilateral spontaneous
pneumothorax, a persistent air leak or
failure to resolve at 5 days, haemothorax,
and divers, pilots and others with an occupational risk.u

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2004 The Medicine Publishing Company Ltd