South African Family Practice 2016; 58(1):19-26

S Afr Fam Pract

Open Access article distributed under the terms of the ISSN 2078-6190 EISSN 2078-6204
Creative Commons License [CC BY-NC-ND 4.0] © 2016 The Author(s)
http://creativecommons.org/licenses/by-nc-nd/4.0
REVIEW

“Alpha-1, are you in? (C)harlie (O)scar (P)appa (D)elta, over!”

GL Muntingh1*

1
Department of Pharmacology, Faculty of Health Sciences, School of Medicine, University of Pretoria
*Corresponding author, email: [email protected]

Abstract
Chronic obstructive pulmonary disease (COPD) is characterised by chronically poor air flow. Typically, it worsens over time.
The main symptoms include shortness of breath, coughing and sputum production. Most people with chronic bronchitis have
COPD. Tobacco smoking is the most common cause of COPD. A number of other factors, such as air pollution and genetics, play a
smaller role. One of the common sources of air pollution is poorly vented cooking and heating fires in the developing world. Long-
term exposure to these irritants causes an inflammatory response in the lungs, resulting in narrowing of the small airways and
breakdown of the lung tissue, leading to emphysema. Genetic involvement, i.e. alpha-1 antitrypsin deficiency, is now a recognised
cause. The diagnosis is based on poor air flow, as measured by lung function tests. In contrast to asthma, the air flow reduction
does not improve significantly with the administration of a bronchodilator. COPD can be prevented by reducing exposure to
known environmental risk factors. This includes an effort to decrease the rate of smoking and to improve indoor and outdoor air
quality. COPD treatment includes stopping smoking, vaccinations, rehabilitation, and often inhaled bronchodilators and steroids.
Some people may benefit from long-term oxygen therapy or lung transplantation. Increased use of medication and hospitalisation
may be needed in those who have periods of acute worsening. Worldwide, COPD effects 329 million people, or nearly 5% of
the population. In 2013, it resulted in 2.9 million deaths, up from 2.4 million deaths in 1990. The number of deaths is projected
to increase owing to higher smoking rates and an ageing population in many countries. New treatments are also emerging
very slowly.

Keywords: AAT, apha-1 antitrypsin, COPD, emphysema, exacerbations, smoking

Introduction

“Cold morning today, doctor”, a 60-year old patient manages

to so say before sitting down with effort, clutching a crumbled
packet of Lucky Strikes in his left hand, complaining that he’s
been coughing for nearly three months now, for two years,
and that this “sputum never stops”. He continues to mumble
something to the effect that his breathing requires effort and
that he feels out of breath and can’t “get enough air in”. The
patient has a pink complexion, his respiratory rate is a little high
and he has pursed lips. Perhaps the diagnosis is smoker’s lung or
“pink puffer”. However, he then explains that sometimes his lips
are blue and that his ankles swell a bit. Could the diagnosis be
“blue bloater”? However, this terminology is no longer accepted
as useful as most patients with chronic obstructive pulmonary
disease (COPD) have a combination of both emphysema and
chronic bronchitis.1,2

History of emphysema

The word “emphysema” is derived from the Greek word, Figure 1: Giovanni Battista Morgagni, who provided one of the earliest
emphusan, and means “puff up” or to “inflate”.3 recorded descriptions of emphysema in 1769

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20 S Afr Fam Pract 2016;58(1):19-26

One of the earliest descriptions of probable emphysema was response in the airways and the lungs to noxious particles or
made in 1679 by Bonet of a condition of “voluminous lungs”. In gases. Exacerbations and co-morbidities contribute to the overall
1769, Morgagni (Figure 1) described lungs which were“turgid, severity in individual patients”.
particularly from air”.4,5
“Chronic bronchitis” is defined as a chronic productive cough
In 1721, the first drawings of this condition were made by for three months in each of two successive years in a patient
Ruysh.5 These were followed with pictures by Baillie in 1789, in whom other causes of chronic coughing, e.g. bronchiectasis,
and descriptions of the destructive nature of the condition. In have been excluded.8 It may precede or follow the development
1814, Badham used “catarrh” to describe the coughing and of air flow limitation.9,10 This definition has been used in many
excess mucus in chronic bronchitis. Laënnec, the physician studies, despite the arbitrarily selected symptom duration.
who invented the stethoscope, used the term “emphysema” in
“Emphysema” is defined by the abnormal and permanent
his book, A treatise on the diseases of the chest and of mediate
enlargement of the air spaces distal to the terminal bronchioles,
auscultation, (1837) to describe lungs which did not collapse
which is accompanied by destruction of the air space walls,
when he opened the chest during an autopsy.
without obvious fibrosis.11 The exclusion of obvious fibrosis was
Laënnec wrote on emphysema: “The disease which I designate intended to distinguish the COPD disease, i.e. definition, clinical
by this title is very little known, and has not hitherto been manifestations, diagnosis and staging alveolar destruction
correctly described by any author. I, for a long time, thought it due to emphysema, from that due to interstitial pneumonia.
very uncommon, because I had observed only a few cases of it. However, increased collagen in the lungs of patients with mild
But since I have made use of the stethoscope, I have verified its COPD has been found in many studies, indicating that fibrosis
existence as well on the living, as on the dead subject, and am led can be a component of emphysema.12,13
to consider it as by no means infrequent. I consider many cases While emphysema can exist in individuals who do not have air
of asthma, usually deemed nervous, as depending on this cause. flow obstruction, it is more common in patients with moderate
The chief reason of this affection having been so completely or severe air flow obstruction.7,14
overlooked is that it is in some sort merely the exaggeration of
the natural condition of the viscus”. Population and epidemiology

Smoking was rare in this era, but it is a fact that emphysema may Worldwide, COPD affects roughly 329 million people, or nearly
occur in non-smokers, particularly with a familial predisposition, 5% of the population.15 In 2013, it resulted in 2.9 million deaths,
or from environmental-provoking factors. Laënnec continued: up from 2.4 million deaths in 1990.7 The number of deaths is
“In opening the chest, it is not unusual to find that the lungs projected to increase owing to higher smoking rates and an
do not collapse, but they fill up the cavity completely on each ageing population in many countries.8
side of the heart. When experienced, this will appear full of air. Globally, roughly 10% of people aged ≥ 40 years have air flow
The bronchus of the trachea are often at the same time a good limitation, i.e. GOLD stage 2 or worse [forced expiratory volume
deal filled with mucous fluid”. Thus, Laënnec had described a in one second (FEV1) ≤ 80% predicted], and up to 25% may
combination of emphysema and chronic bronchitis!4 have GOLD stage 1 (FEV1 ≥ 80% predicted, but FEV1/forced
The term “chronic bronchitis”came into use in 1808, while the term vital capacity ≤ 0.7). It is also suspected that up to 60–85% of
people with COPD with mostly mild or moderate severity are
COPD was first believed to have been used in 1965.1,4 Previously,
undiagnosed.16
it was known by a number of different names, including chronic
obstructive bronchopulmonary disease, chronic obstructive The disease affects men and women almost equally, as there has
respiratory disease, chronic air flow obstruction, chronic air been increased tobacco use in women in the developed world.
flow limitation, chronic obstructive lung disease, non-specific The global numbers are expected to continue to increase as risk
chronic pulmonary disease and diffuse obstructive pulmonary factors remain common and the population continues to get
syndrome. The terms “chronic bronchitis” and “emphysema” were older.17
formally defined in 1959 at the CIBA guest symposium, and in
COPD is considered to be the fourth leading cause of death
1962 at the American Thoracic Society Committee meeting on
worldwide. Mortality associated with COPD is rising, while that
diagnostic standards.6
linked to cardiovascular disease is falling. COPD is expected to be
Definition the third leading cause of death in the next 15–20 years.16

COPD is defined as follows by the Global Initiative for Chronic Causes

Obstructive Lung Disease (GOLD), a project initiated by the
Tobacco smoke is the primary cause of COPD, with occupational
National Heart, Lung and Blood Institute (NHLBI) and the World
exposure and pollution from indoor fires being a significant
Health Organization (WHO):7
contributing factor.18 A number of industries and sources have
“COPD, a common preventable and treatable disease, is been implicated, including high levels of dust in coal mining,
characterised by air flow limitation that is usually progressive, gold mining and the cotton textile industry, occupations which
and associated with an enhanced chronic inflammatory involve cadmium and isocyanates, and fumes from welding.19

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“Alpha-1, are you in? (C)harlie (O)scar (P)appa (D)elta, over!” 21

Working in agriculture is also a risk.20 Typically, this exposure varying degrees in virtually everyone with COPD. The reasons for
occurs over several decades before symptoms develop.18 these variable phenotypes and their clinical importance are not
that well understood.
A person’s genetic make-up also affects the risk.18 It is more
common in relatives of those with COPD who smoke than Chronic poorly controlled COPD can lead to hypoxia, which
in unrelated smokers.3 Currently, the only clearly inherited occurs from poor gas exchange due to decreased ventilation
risk factor is alpha-1 antitrypsin (AAT) deficiency. This risk is from airway obstruction, hyperinflation and a reduced desire
particularly high if someone deficient in AAT also smokes. AAT to breathe.3 Airway inflammation is also increased during
inhibits a wide variety of proteases. It protects tissue from the exacerbations, resulting in increased hyperinflation, reduced
enzymes of inflammatory cells, especially neutrophil elastase. expiratory air flow and worsening of the gas transfer. This can
In its absence, i.e. in ATT deficiency, neutrophil elastase is free also lead to insufficient ventilation, and eventually hypoxia. If
to break down elastin, which contributes to the elasticity of the present for a prolonged period, it can result in narrowing of the
lungs, resulting in respiratory complications such as emphysema
pulmonary arteries, while emphysema leads to the breakdown
or COPD in adults, and cirrhosis in adults or children.21
of capillaries in the lungs. Both these changes result in increased
It is responsible for roughly 1–5% of cases, and the condition blood pressure in the pulmonary arteries, placing the patient at
is present in 3–4 in 10 000 people.21,22 Other genetic factors are increased risk of developing cor pulmonale.3
being investigated, of which there are likely to be many.20
Management
Acute exacerbations
There is no known cure for COPD, but the symptoms are
Acute exacerbations of COPD, also known as acute exacerbations treatable, and its progression can be delayed. The major goals of
of chronic bronchitis, signify a sudden worsening of the COPD management are to reduce the risk factors, manage stable COPD,
symptoms, i.e. shortness of breath, and the quantity and colour prevent and treat acute exacerbations and manage associated
of the phlegm, which typically lasts for several days. It may illnesses.28
be triggered by an infection with bacteria or viruses, or by
environmental pollutants. At times, the cause or reason is simply Other recommendations include an influenza vaccination once
not known. Improper use of medication can also lead to this.23 a year, a pneumococcal vaccination once every five years, and
reduction in exposure to environmental air pollution.27 Palliative
Infections appear to be the cause in 50–75% of cases,23,24 with care may reduce the symptoms in those with advanced disease.
bacteria in 25% (including Haemophilus influenzae, Streptococcus Supplemental oxygen has been shown to slow the progress
pneumoniae and Moraxella catarrhalis), viruses in 25% of this disease. It has now been shown that giving morphine
(rhinovirus, coronavirus and parainfluenza), and both in 25%. improves the feelings or sensations of shortness of breath.
Cold temperature may also play a role. Exacerbations occur more Noninvasive ventilation may be used to support breathing.29
commonly in winter.25
Nonpharmacological
Those with more severe underlying disease have more frequent
exacerbations of 1.8 per year with mild disease, 2–3 per year with First and foremost, it is important to quit smoking. Keeping
moderate disease, and 3.4 per year with severe disease. Those people from starting to smoke is a key aspect of preventing
with many exacerbations have a faster rate of deterioration of COPD. Stopping smoking in those who smoke is the only measure
their lung function.26 Congestive heart failure and pulmonary that has been shown to slow the progression of COPD.30 Even at a
emboli can worsen symptoms in those with pre-existing COPD.27 late stage of the disease, it can reduce the rate of worsening lung
function and delay the onset of disability and death. Stopping
Pathophysiology
smoking decreases the risk of death by nearly 18%.27
COPD is an obstructive lung disease in which chronic
Exercise
incompletely reversible poor air flow (air flow limitation) and the
inability to breathe out fully (air trapping) exist.27 This develops A programme with the aim of pulmonary rehabilitation should
as a significant and chronic inflammatory response to inhaled include coordinated aspects of exercise, disease management
irritants.1 Chronic bacterial infections may also add to this and counselling.19 Pulmonary rehabilitation appears to improve
inflammatory state.26 The inflammatory cells involved include overall quality of life and the ability to exercise, and reduce
neutrophil granulocytes and macrophages. Those who smoke mortality in those who have experienced a recent exacerbation.31
additionally have cytotoxic  T lymphocyte involvement, and However, breathing exercises by themselves appear to play
some patients with COPD have eosinophil involvement, similar
a limited role.18 Some authors have shown that pursed lip
to that in asthma.
breathing exercises may be useful.16
COPD is characterised by both the destruction of lung
Lung volume reduction surgery
parenchyma with loss of elastic recoil (causing emphysema), and
infiltration of the walls of the small airways by inflammatory cells Consideration of lung volume reduction surgery is recommended
(causing chronic bronchiolitis or bronchitis. These two broad in all patients with very severe COPD. The surgery provides
phenotypes are distinct entities, and they coexist and overlap in a  mortality reduction  and improvement in quality of life,
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22 S Afr Fam Pract 2016;58(1):19-26

especially in patients with upper lobe-predominant disease and • An improvement in post-bronchodilator FEV1, i.e. ~50–100 ml.
poor exercise capacity or ability.32 • An improvement in dyspnoea, i.e. ~3 points using the
Non-surgical, bronchoscopic lung volume reduction St George’s respiratory questionnaire.
• A reduction in daily, short-acting beta agonist use by
Because of the morbidity and risk associated with lung volume
~1 inhalation.
reduction surgery, and its subsequent unpopularity, numerous
• The prevention of COPD exacerbations was better with
companies and investigators have sought to produce a medical
tiotropium than salmeterol in  one randomised trial, but the
device that could be placed bronchoscopically, and which would
effect was quite small.35
reduce dead space ventilation, i.e. lung volume reduction surgery
without the surgery. To date, none of these devices have worked Long-acting beta agonists (LABAs) have a cardiac effect, but
effectively enough for their use to be recommended outside have not been found to cause cardiovascular events, and don’t
clinical trials. The most recent example was bronchoscopic lung have the very slightly increased risk of death associated with
volume reduction in the Exhale Airway Stents for Emphysema LABA monotherapy for asthma.
(EASE) trial, in which it was demonstrated that bronchoscopically
Tiotropium has been suspected of causing cardiovascular events
placed airway stents with a one-way valve did not improve
based on observational trials, but the current consensus [based
airway mechanics or dyspnoea.
mainly on Understanding Potential Long-term Impacts on
Perhaps collateral ventilation or interalveolar air drift through Function with Tiotropium (UPLIFT) randomised trial data and a
the pores of Kohn are the most likely answers to this failure or meta-analysis] is that it does not cause cardiovascular events.36
ineffectiveness. These are miniscule anatomical intercommuni-
Methylxanthines
cations which allow air to fill back into emphysematous areas
after air has been removed through the implanted device.32 The use of theophylline was summarised in a review carried out
by Vaz Fragoso as follows. Theophylline may favourably affect the
Pharmacological
major factors associated with functional impairment in COPD,
The GOLD guideline treatment table is the most well-known and such as dyspnoea, exercise capacity, respiratory mechanics and
accepted guideline for the treatment of COPD. It is summarised respiratory muscle strength. Theophylline is generally considered
in Table 1.16  to be a third-line bronchodilator drug in chronic COPD, after
inhaled anticholinergics and beta 2 agonists.
Bronchodilators
Despite both smoking cessation and the use of inhaled
Inhaled bronchodilators are the primary medication used, and
bronchodilators, theophylline may reduce functional impairment
result in a small overall benefit.4,33 There are two major types,
and exacerbation frequency in patients with persistent functional
β2 agonists and anticholinergics. Both exist in long- and short-
impairment, but the effect in individual patients is variable. In
acting forms. They reduce shortness of breath, wheezing and
general, patients with COPD can be adequately treated with
exercise limitation, resulting in improved quality of life.34 It is
serum levels in the 8–12 µg/ml range. Once an appropriate
unclear whether or not they change the progression of the
serum level has been achieved, subsequent measurements can
underlying disease.27
be made at 6- to 12-month intervals, or if the patient’s clinical
Long-acting bronchodilators (formoterol and salmeterol), and status or concomitant medications change. When compared
long-acting anticholinergics (tiotropium), have similar efficacy, to acute intoxication, chronic theophylline overmedication is
including: associated with a greater frequency of major toxicity, occurs at

Table 1: The Global Initiative for Chronic Obstructive Lung Disease guideline for the treatment of chronic obstructive pulmonary disease

Stage* Mild (1) Moderate (2) Severe (3) Very severe (4)
FEV1/FVC ≤ 0.70 ≤ 0.70 ≤ 0.70 ≤ 0.70
FEV1 ≥ 80% predicted 50–80% predicted 30–50% predicted ≤ 30% predicted, or ≤ 50% predicted
with chronic respiratory failure
Treatment Short-acting bronchodilator, as needed, for all patients with COPD
Consider pulmonary Consider pulmonary rehabilitation Consider pulmonary rehabilitation
rehabilitation
One or more long-acting One or more long-acting One or more long-acting
bronchodilators bronchodilators bronchodilators
Inhaled corticosteroid, if there are Inhaled corticosteroid, if there are
repeated exacerbations repeated exacerbations
Long-term oxygen, if needed.
Consider lung volume reduction
surgery
* All patients should receive smoking cessation counselling and an influenza vaccination
COPD: chronic obstructive pulmonary disease, FVC: forced vital capacity, FEV1: forced expiratory volume in one second

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“Alpha-1, are you in? (C)harlie (O)scar (P)appa (D)elta, over!” 23

relatively lower theophylline levels, and cannot be predicted by • Oxygen and ventilatory support for respiratory failure. A recent
the peak serum theophylline concentration. review showed that noninvasive positive pressure ventilation
was likely to improve outcomes from COPD exacerbations.
Methylxanthines are not recommended for routine management
in acute COPD exacerbations. In addition to a lack of efficacy in • Considering theophylline for severe exacerbations.
this setting, methylxanthines increase the likelihood of side- • Adding oral corticosteroids, if bronchodilators are not
effects, e.g. nausea, vomiting and arrythmias. 37 successful.
• Treating most COPD exacerbations with 40 mg prednisone for
Corticosteroids
five days, i.e. the 2014 GOLD guidelines. This was a significant
Corticosteroids are usually used in inhaled form, but may also change from the previous recommendation of 10–14 days. As
be used orally to treat and prevent acute exacerbations. While discussed previously, five days of steroids was suggested as
inhaled corticosteroids have not shown benefit in people with adequate treatment for COPD exacerbations in most patients
mild COPD, they decrease acute exacerbations in those with in the REDUCE study.43
either moderate or severe disease. 38
• Antibiotics are indicated in a patient with increased sputum
Interestingly, in the Reduction in the Use of Corticosteroids in production, purulent sputum, increased dyspnoea and an
Exacerbated COPD (REDUCE) trial, it was demonstrated that a elevated white count, or who is febrile. 44
longer course of oral prednisone did not reduce the rate of repeat The choice of antibiotics is also dependent upon the severity of
COPD exacerbations. Fifty-seven patients taking prednisone for the symptoms. “Simple” COPD generally refers to a person aged ≤
14 days had a repeat COPD exacerbation (37%), compared to 65 years, with fewer than four exacerbations per year, minimal or
56 taking prednisone for 5 days (36%). Extra prednisone did not moderate impairment in respiratory function and no co-morbid
prolong the time to the next COPD exacerbation.39 An important disease. Therapy in patients with “simple” COPD should target
consequence of this was reduced corticosteroid exposure, and H. influenzae, M. catarrhalis and S. pneumoniae, and possibly
thus the side-effects. pathogens of atypical pneumonia.The first-line treatment is a
When used in combination with a LABA, they decreased mortality beta-lactam antibiotic, such as amoxicillin. The choice depends
more than either an inhaled corticosteroid or a LABA alone.40 upon resistance patterns.
They have no effect by themselves on overall one-year mortality, More complicated bronchitis occurs when the patient is aged ≥
and are associated with an increased rate of pneumonia.41 65 years, has four or more exacerbations per year, a FEV1:FVC ratio
It is unclear whether or not they affect the progression of the of less than 50% on spirometry, has failed to respond to previous
disease.4 Long-term treatment with an oral glucocorticoidsteroid antibiotic treatment, and/or has co-morbidity. Treatment in these
is associated with significant side-effects.41 cases should target Gram-negative bacteria. The possibility of
Inhaled corticosteroid and LABA combination products high antibiotic resistance should be considered. Sputum culture
cause pneumonia in a tiny proportion of patients. However, results are of great value in determining antibiotic resistance.
combination products may also reduce mortality slightly, based The first-line treatment is cefuroxime or co-amoxiclav. Third-line
on the just barely negative Towards a Revolution in COPD Health treatment, as well as treatment in penicillin-allergic patients, is a
(TORCH) trial. Inhaled corticosteroid/LABA combination products fluoroquinolone, such as ciprofloxacin. An agent active against S.
do not seem to cause increased risk of death from pneumonia. pneumoniae may have to be added.45
Even when inhaled, corticosteroids probably cause osteoporosis Replacing enzymes
in a small number of susceptible patients.
AAT-deficient individuals who have, or show signs of developing,
The evidence is inconclusive as to whether any drug treatments significant emphysema, can be augmented with a pooled,
for COPD modify (slow) the disease course or reduce mortality, purified, human plasma protein concentrate replacement for the
but data from several clinical trials suggests that both inhaled missing enzyme. Practitioners should immunise patients against
corticosteroid/LABA combination products and tiotropium hepatitis regardless.
may lessen a decline in FEV1 and slightly reduce mortality risk.
In fact, better outcomes from “triple therapy”, i.e. an inhaled Weekly intravenous infusions of AAT protein concentrates restore
corticosteroid, a long-acting beta-agonist and tiotropium serum and alveolar AAT concentrations to protective levels.
given together, were suggested in an  observational study  on It has not been proved in any controlled studies that intravenous
symptomatic patients with severe to very severe stable COPD.42 augmentation therapy improves survival or slows the rate of
Treatment emphysema progression. Results from the National Institutes
of Health (NIH) patient registry and a comparison of Danish and
Guidelines are available for the treatment of COPD exacerbations. German registries have been published, and both suggest that
They mainly recommend: augmentation therapy has beneficial effects. Although they
• Increasing the dose of short-acting bronchodilators, i.e. were not controlled treatment trials, the similarity of the results
albuterol and/or ipratropium. suggests that the findings are significant.
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24 S Afr Fam Pract 2016;58(1):19-26

The NIH report described an overall death rate 1.5 times higher randomised to take either azithromycin 250 mg or placebo
for those who did not receive augmentation therapy and a daily for one year, those taking azithromycin experienced fewer
rate of FEV1 decline (54 ml/year) in AAT-deficient individuals, exacerbations, described as follows:47
roughly twice that of healthy non-smokers, but approximately • There was a 27% reduction in exacerbations.
50% that of smokers (108 ml/year). Augmentation therapy did
• There was a delay of 92 days in median time to the first
not improve the average FEV1 decline (54 ml/year). However,
exacerbation (174 vs. 266 days).
participants with moderate air flow obstruction (FEV1 35–60% of
the predicted value) experienced a slower rate of decline, i.e. a • According to the St George’s respiratory questionnaire, quality
mean difference of 27 ml/year). of life improved by 2.8 points vs. 0.6 (with 4 being accepted as
“clinically significant”).
Augmentation therapy is recommended in the current
guidelines for individuals with abnormal AAT genotypes, who However, sadly, at least 32 more people in the azithromycin
have AAT levels below 11 μm and documented evidence of air group experienced hearing loss (142 vs. 110), and hearing did
flow obstruction in pulmonary function tests.46 not return to baseline on repeat testing in most.

While firm guidelines have not been developed with respect to Conclusion
initiating or continuing augmentation therapy, most pulmonary
physicians require the serum level to be below the threshold COPD, whether chronic or acute, is a very distressing debilitating
protective value, and the patient to have one or more of the condition. Acute exacerbations can be partially prevented. Some
following: signs of significant lung disease, such as chronic infections can be averted by vaccination against pathogens
productive cough or unusual frequency of lower respiratory such as influenza and S. pneumoniae. Regular medication
infection, air flow obstruction, accelerated decline of FEV1, use can prevent COPD exacerbations. LABAs, long-acting
or chest radiographic or computed tomography evidence of anticholinergics and inhaled corticosteroids (“triple-therapy”)
emphysema.46,47 are now emerging as a very useful approach to managing COPD
and reducing exacerbations. Important methods of prevention
Some interesting developments
include smoking cessation; avoiding dust, passive smoking
The role of the new phosphodiesterase-4 inhibitors (not and other inhaled irritants; and yearly influenza and five-year
properly discerned yet) has been the focus of relative recent pneumococcal vaccinations. Promising avenues for treating AAT
new developments. Cochrane published an  analysis  on these deficiency exist.
new agents in 2011. Roflumilast, and its sibling, cilomilast, only
Regular exercise, appropriate rest and healthy nutrition are
improved post-bronchodilator FEV1 by ~50 ml, and reduced
exacerbation frequency by a relative 17%, in selected patients advocated, as well as avoiding people who are currently infected
with GOLD stage 3–4 COPD who experienced coughing with with a cold or influenza, maintaining good fluid intake, and lastly,
sputum changes and had a history of exacerbations. humidifying the home, in order to help reduce the formation of
thick sputum and chest congestion.
However, patients reported that these medications only
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