COPD: Anaemia Is An Independent Risk Factor For Reduced Functional Capacity

Anaemia is a condition affecting patients who suffer from a variety of chronic illness. It has been found to be present in people with congestive heart failure, arthritis, cirrhosis of the liver, kidney failure and AIDS among others. Chronic obstructive pulmonary disease or COPD is also a chronic illness affecting adults. Although it is a disease of the lungs, it is also one that has important systemic consequences.


Because of the close relationship between oxygenation and haemoglobin (Hb) production and the fact that prior to the widespread use of oxygen to treat the hypoxia of severe COPD many patients had increased Hb (polycythaemia), it has been assumed that anaemia was a rare occurrence among these people.
However, as COPD is associated with inflammation it has become possible that the levels of Hb are abnormal in the patients as we see them today.



To answer that question, Claudia Cote (Dept of Medicine, Respiratory Disease Section, Bay Pines VAMC, Florida, USA) and her colleagues have investigated the prevalence and association of abnormal Hb with clinical outcomes.


Analysis of a prospective cohort of 683 stable COPD outpatients in a US Veterans Administration pulmonary clinic was performed.


The results show that anaemia is present in 116 (17%) and polycythaemia in 40 (6%) patients. While the only value that differs between polycythaemic and non-polycythaemic patients is mean Hb, anaemic patients have a significantly higher sensation of shortness of breath, lower capacity to exercise and shorter median survival (49 vs 74 months) than non-anaemic patients. Anaemia independently predicts dyspnoea and reduced exercise capacity.



The American team concludes that anaemia in COPD is an independent risk factor for reduced functional capacity. Polycythaemia prevalence is low and has no association with worsened outcomes. Further work is required to evaluate the effect of anaemia correction on outcomes in COPD.



"Haemoglobin level and its clinical impact in a cohort of patients with COPD"

European Respiratory Journal (ERJ)

News From The September Issue Of Chest

PEDIATRIC CHRONIC COUGH LINKED TO REFLUX AND ALLERGIES


New research shows that chronic cough in children is most often caused by gastroesophageal reflux
and allergies. Researchers from Tulane University in New Orleans, LA, evaluated 40 patients aged 5 to
12 years with chronic cough (> 8 weeks in duration) with no obvious cause. Each patient underwent
extensive multispecialty testing. Results showed that reflux was the single most commonly associated
factor of chronic cough by itself (27.5 percent), followed by allergy (22.5 percent). All patients
received treatment for their underlying conditions, and all responded to their respective treatments.
This study is published in the September issue of CHEST, the peer-reviewed journal of the American
College of Chest Physicians.



STATINS MAY BENEFIT PATIENTS WITH COPD



Statins have been shown to benefit patients with cardiovascular disease and high cholesterol, but now
research shows that statins may provide significant benefits for patients with chronic obstructive
pulmonary disease (COPD). Researchers from the University of British Columbia reviewed data from
nine studies that illustrated the beneficial effects of statins on patients with COPD. Further analysis
showed that each study provided at least one benefit to patients with COPD, including reduced
exacerbations (3 studies); reduction in the number of COPD-related intubations and time to COPDrelated
intubations (1 study); improved pulmonary function (1 study); improved exercise capacity (1
study); improved mortality (2 studies); and improved all-cause mortality (3 studies). Researchers
conclude that, although statins show promise for patients with COPD, additional research is needed.
The article is published in the September issue of CHEST, the peer-reviewed journal of the American College of Chest Physicians.



PATIENTS WITH INTERSTITIAL LUNG DISEASE NEED NOT AVOID AIR TRAVEL



Patients with interstitial lung disease (ILD) are often concerned about the occurrence of pneumothorax
(collapsed lung) or other life-threatening events during air travel. However, new research shows that,
even in ILD with a high prevalence of spontaneous pneumothorax, such as lymphangioleiomyomatosis
(LAM), there is a relatively low risk of these events occurring. Researchers from the National
Institutes of Health reviewed records and imaging studies of 449 patients with sarcoidosis, idiopathic
pulmonary fibrosis, and LAM, who made a total of 816 trips by airplane and 416 trips by land. Results
showed that the frequency of pneumothorax in patients with LAM was 2.9 percent in those who
traveled by airplane and 1.3 percent in those who traveled by ground transportation. No patients with
IPF or sarcoidosis had a new pneumothorax while traveling. Researchers conclude that, in patients
with LAM, the presence of pneumothorax associated with air travel may be related to the high
incidence of pneumothorax from the disease itself and not to travel. This article is published in the
September issue of CHEST, the peer-reviewed journal of the American College of Chest Physicians.

Chronic Obstructive Pulmonary Disease: Hospital Readmissions Could Be Reduced

Readmission of patients with chronic obstructive pulmonary disease (COPD) is a major problem within health systems. Each admission for exacerbation worsens the patient's quality of life and, at the same time, presents an economic challenge for the hospital centre. A study published in the European Respiratory Journal describes the usefulness of an integrated and coordinated intervention of primary health care and hospital health care. This work, which demonstrates the benefits of cooperation among several health care levels, has been led by Dr. Josep Roca and Mrs. Carme Hernandez, members of the IDIBAPS Physiopathological Mechanisms of the Respiratory Disease Group and of the Pneumology Unit of Hospital Cl?­nic.



This study includes 150 patients, 65 of which receive integrated health care. Results show that more than a half of these patients do not need readmission, whereas 67% of patients receiving conventional health care are readmitted in hospital. Previous studies assessing home health care did not obtain conclusive results. The main limitations were the lack of standardisation of the interventions and the lack of homogeneity of patients. In this new work, highly precise criteria for the inclusion of patients have been defined, and intervention protocols have been highly detailed. Protocols were not identical in both countries participating in the study, what reinforces the positive results obtained. Differences among both countries have permitted to conclude that a higher number of home health care appointments does not imply better results on the health of patients. The Belgian system implied more home care assistance than the Catalan system, but no differences were observed in the results. This works is presented as a conclusion of the European project CHRONIC, a pioneer European telemedicine research project started on January 2000 that closes with this publication.



The design of integrated health care of these initiatives makes health specialists much more accessible to patients, primarily thanks to an only telephonic switchboard for these patients. Furthermore, COPD patients receive an informative course on their disease, which gives them more autonomy. Results of this study are along the same line of those obtained with the Home Care Programme promoted by Hospital Clinic during the first trimester of 2006 aimed to patients with COPD and cardiac insufficiency. Patients included in this programme evolved from a 9-day admission to a 2-day admission. This programme, which emphasizes specialised nursing and medical cooperation, was initially supported by CATSalut, but now and until 31 December the project will be supported by Hospital Clinic. Home care health reflects the fructuous relationship between hospital care and research in Hospital Clinic, and could be a major tool of health management in several chronic diseases in the future. 60% of patients admitted in emergencies have a chronic pathology; therefore, the fact of giving assistance to these patients at the correct health care levels can be a decisive factor in third level hospitals, such as Hospital Clinic, in order not to collapse the centre.







Contact: Alex Argemi


IDIBAPS - Institut d'Investigacions Biomediques August Pi i Sunyer

Wrinkled Middle-Aged Smokers At Higher Risk Of COPD

If you are middle-aged, have lots of wrinkles and smoke, you are five times more likely to develop CPOD (chronic obstructive pulmonary disease) than middle-aged smokers who are not very wrinkly, says a study from the Royal Devon and Exeter Hospital, UK.


You can read the report in the journal Thorax. The scientists said that the heavy lines on a smoker's face could provide a good indication of COPD risk. They studied 149 people and concluded that genetic propensity to wrinkles seems to come with a higher susceptibility of developing COPD.


Millions of people around the world have COPD and have not been diagnosed. It is caused mainly by smoking. WHO predicts it will become the third leading cause of death in the world within the next 14 years.


The study looked at 149 people who smoke, or used to smoke. They were aged 45-70 and all came from the Cambridge, UK, area. 68 of them had COPD. 25 of them had very wrinkly faces, of which 21 had COPD. The researchers found that after taking into account the people's age and how long they had been smokers, those with wrinkly faces had five times the probability of having COPD compared to smokers who did not have wrinkly faces. Severe emphysema was also linked to wrinkly faces, said the researchers.


Team leader, Dr Bipen Patel, said "We think there is a genetic susceptibility to COPD. What this research shows is that those who are prone to COPD are also prone to wrinkles. If there is a gene for COPD susceptibility, it may also increase the chance of someone developing wrinkles." He added that wrinkles may become a risk indicator for COPD.


As early diagnosis is an essential part of effective COPD treatment, perhaps doctors should look out for middle-aged smoking patients who have wrinkly skin.

Air Travel and Lung Disease: Current Guidelines Are Inappropriate

For the first time, patients suffering from chronic obstructive pulmonary disease (COPD), were studied during a
commercial flight lasting almost six hours. Their blood oxygen content underwent a considerable reduction, more marked than
could have been predicted using the currently accepted guidelines. However, the oxygen reduction was generally well tolerated
by those subjects who, prior to departure, had a blood oxygen content equal to or greater than the recommended pre-flight
value.


A German team, whose study also appears in April's ERJ, conducted similar experiments on patients with cystic fibrosis. They
conclude that these patients can also travel on flights of several hours' duration without excessive risk.




What, in today's world, could be more commonplace than a plane trip lasting a few hours, whether for business or pleasure?
Yet, while such flights are unproblematic for most of us, they can be dangerous for people with certain conditions. This is
particularly true of lung disease sufferers, especially those with either chronic bronchitis (known to doctors as chronic
obstructive pulmonary disease or COPD) or cystic fibrosis. Under scrutiny, therefore, is the air pressure on board commercial
aircraft, whose passengers are subjected to a virtual altitude of 1,500 to 2,500 metres depending on the length of flight. At
such altitudes, the air contains some 30% less oxygen, a matter not to be taken lightly for patients whose blood oxygen level
is already precarious because of their respiratory condition.



For several years, doctors have been working on this issue and trying to develop recommendations, both on the minimum oxygen
level needed inside planes and on methods for identifying, in advance, patients who could encounter problems while flying.
These methods include respiratory capacity measurement and assessment of whether the subject can walk fifty metres without
getting excessively breathless. Measurement of arterial oxygen tension (PaO2) was also recommended: above a certain value, it
was deemed to indicate that the level would remain acceptable during the flight.



Real flight conditions



In fact, these various recommendations have created quite a lot of debate, especially since they partially contradict one
another.


So four Norwegian doctors decided to undertake a study in the conditions of a real flight. Their results can be seen in
April's issue of the ERJ, the scientific publication of the European Respiratory Society (ERS).


While most of the existing data came from experimental studies based either on inhalation of air with artificially reduced
oxygen levels or on time spent in a depressurised caisson, the Oslo team took an innovative approach and conducted a study on
board a real commercial flight.















The researchers decided to assess the effects of oxygen-reduced air on 18 COPD patients during a flight from Oslo to Las
Palmas (five hours and forty minutes in duration) with the cabin pressure equivalent at cruising height to an average
altitude of 1,829 metres (6,000 feet).



"The experimental nature of the earlier studies made it impossible to incorporate the various stresses that travellers
encounter during their journey: the need to carry luggage, the often lengthy trek to the departure gate, the cramped
conditions in the plane, the dryness of the cabin air, turbulence and other factors", explains Aina Aker???, the article's main
author.


"But our work has been able to include all of these elements, and we have also studied the influence of hypoxia duration by
taking measurements twice during the flight", adds Ole Henning Skj???nsberg, Aker???'s colleague at the Department of Pulmonary
Medicine of Ullev???l University Hospital, Oslo.



Rigorous selection of subjects



The Norwegian researchers set themselves two goals: to measure various parameters during the flight and to compare the values
measured on the ground before the journey with those obtained in the air.


First, they measured the various dissolved gases and the oxygen saturation in the subjects' arterial blood, noting possible
clinical manifestations, such as when the subjects moved around the aircraft cabin.


These measurements were taken twice during the flight: approximately one hour after the plane reached cruising height, and
three hours later, following a light meal without alcohol.


Aker??? and her colleagues also looked at whether certain parameters connected with the respiratory volumes and blood gases
measured prior to departure could be correlated with the data registered in-flight, and, if so, whether they allowed
prediction of what would happen during the journey.


The 18 patients (five women and 13 men, aged 49 to 73) were recruited through a lung rehabilitation centre that organises
rehabilitation programmes in warmer climates specially designed for people with chronic bronchitis or emphysema.


An important detail: the subjects selected had not suffered an exacerbation for at least two months, and all but one used
bronchodilators. Additionally, to avoid any risk of misinterpretation, they had to be clear of any symptoms that could
suggest cardiac or neurological compromise, any lung disease other than their COPD and anaemia.



Risk of fatigue after five hours



"We had, of course, made sure that the rehabilitation centre had pronounced all of our subjects fit to fly without additional
oxygen", the authors explain, "and that they could all walk at least fifty metres without excessive breathlessness, which we
verified with a treadmill test."


After an hour at cruising height, the investigators found a considerable drop in blood oxygen pressure (averaging 20%),
while, quite logically, arterial oxygen saturation had decreased from 96???1% before departure to 90???4% in-flight. This held
true while subjects remained seated; moving around the cabin caused arterial oxygen saturation to fall even more, to
87???4%.



The Norwegian team also measured arterial carbon dioxide pressure and found it to fall slightly after the first hour of
flying, in parallel with a marked rise in heart rate.


"The reduction observed after four hours of flying constitutes in our view evidence of a compensatory hyperventilation
developed by subjects to maintain their arterial oxygen saturation", Skj???nsberg comments. "This could indicate that such
patients may be at risk of respiratory fatigue during longer flights."


Comparison of pre- and in-flight data revealed a number of correlations and confirmed that arterial oxygen pressure on the
ground can allow prediction of in-flight values. However, the Norwegian team's measurements show that the current guidelines
are inappropriate.


For example, the guidelines assume that arterial oxygen pressure will be adequate if, before departure, it exceeds a certain
level (9.3 kiloPascals), yet four patients meeting that criterion had an in-flight oxygen saturation of below 84%. Five
others who met the criterion complained of mild breathing difficulties during the flight - even though they remained seated -
and eight more experienced symptoms when moving around the cabin.


The Oslo researchers emphasise, though, that the rarefaction was well tolerated by most of the patients, and only one
presented severe breathlessness at rest, which was further exacerbated during movement around the cabin.



What about cystic fibrosis patients?



The same questions apply to patients with another very disabling lung disease, cystic fibrosis, who need or wish to travel by
air. The news is good for those patients too, according to another study also published in April's ERJ.



A team from Munich University, led by Rainald Fischer, examined lung function, arterial blood gases and respiratory symptoms
in 36 cystic fibrosis sufferers under simulated air travel conditions.


Following tests in Munich (approximately 500 metres above sea level), the patients were reviewed a fortnight later after
spending seven hours in a laboratory in the Bavarian Alps, at an altitude of 2,650 metres.



As with the COPD patients, arterial oxygen pressure fell significantly at the higher altitude. A third of the subjects were
found to have values below 6.6 kPa, which is the minimum value recommended by US and British guidelines for obstructive
pulmonary disease sufferers using commercial flights.


Likewise, the German team also found that the fall was greater during physical exertion (on an exercise bicycle), but only
one patient complained of feeling unwell during such exertion.
So the German team can conclude that cystic fibrosis patients with a ground PaO2 of more than 8 kPa are perfectly capable of
tolerating, for several hours, an altitude equivalent to that found in the cabin of a commercial aircraft. Nevertheless,
Fischer and colleagues suggest to include results of spirometry (e.g. FEV1) in future guidelines, in order to emphasise the
role of bronchial obstruction in a hypoxic environment.


Which means there is no automatic reason to forbid such patients the joys of far-flung adventures.



EUROPEAN RESPIRATORY JOURNAL (ERJ), Vol. 25, No 4

erj.ersjournals

Lungs Try To Repair Damaged Elastic Fibers

The lungs of patients suffering chronic obstructive pulmonary disease (COPD) attempt to repair damaged elastic fibers, a new finding that contradicts the conventional wisdom on the capabilities of the adult lung.


The study "Evidence for attempted regional elastic fiber repair in severe emphysema," was done by Jason Woods, Kristin Castillo, Alexander Patterson and Richard Pierce of Washington University, St. Louis, Mo.; Joel Cooper of the University of Pennsylvania, Philadelphia; and James Hogg of St. Paul's Hospital, Vancouver, British Columbia. The authors will be present their findings Nov. 3 at The American Physiological Society conference "Physiological Genomics and Proteomics of Lung Disease."


The researchers found that synthesis of elastin, a gene linked to elastic fiber growth, is increased in the moderately diseased tissue of COPD patients.
Elastic fibers allow the lung to expand and contract with breathing.


"We've found elastin synthesis to increase in the air sacs (alveoli) and airways of the lungs of patients suffering severe or end-stage COPD," Woods explained. "This shows that the lung may be attempting to repair itself."


The finding is important because it could pave the way to develop a drug to 'turn on' key genes to allow the lung to grow new alveoli, he said. Alveoli play a role in the exchange of oxygen and carbon dioxide between the lungs and the circulatory system.


A 2-year-old could do it


Very young children who suffer lung injuries increase elastin expression and produce new elastic fibers inside the alveoli, Woods said. Adults do not have that ability and that has led physiologists to conclude that the elastin gene must shut off after we reach a certain age, ending elastin fiber production.


Physiologists want to understand this process in the hope that it could be harnessed to repair the diseased adult lung. In particular, Woods and his colleagues looked at three genes associated with elastic fiber assembly:
Emilin-1, MFAP2 and elastin. They found the expression of elastin consistently increased in the diseased lungs they studied.


In a preliminary study, the researchers examined two diseased lungs removed from end-stage COPD patients undergoing lung transplants. COPD develops as a result of exposure to toxins such as cigarette smoke, resulting in inflammation to the small airways and destruction of elastic fibers within alveoli. The patients suffered from emphysema.


The team used hyperpolarized magnetic resonance imaging (MRI) to characterize the regions of the lung showing moderate emphysema and regions showing severe emphysema. They found that new elastin synthesis was initiated in moderately diseased specimens.


The researchers did a second study using 10 lungs from end-stage COPD patients who had undergone transplants. Again, they found the greatest amount of elastin gene expression in the moderately diseased areas of the lungs, Woods said. There was no variability in elastin levels within the control lungs.


Further, the team found that the increase in elastin expression occurred on the alveolar walls, the same area where elastin occurs during the lung's development in children. This shows the lung is attempting to repair the elastic fibers in end-stage emphysema, the authors concluded.


Funding


National Institutes of Health (Pierce) and the Barnes-Jewish Foundation
(Woods)


The American Physiological Society was founded in 1887 to foster basic and applied bioscience. The Bethesda, Maryland-based society has 10,500 members and publishes 14 peer-reviewed journals containing almost 4,000 articles annually.


APS provides a wide range of research, educational and career support and programming to further the contributions of physiology to understanding the mechanisms of diseased and healthy states. In 2004, APS received the Presidential Award for Excellence in Science, Mathematics and Engineering Mentoring.


American Physiological Society

Budesonide/formoterol Plus Tiotropium Improves The Quality Of Life Of Patients With Severe COPD

Preliminary results from a double-blind, randomised, multicentre trial among 660 patients with chronic obstructive pulmonary disease (COPD) show that budesonide/formoterol (Symbicort®: AstraZeneca) plus tiotropium (Spiriva™: Boehringer Ingelheim Limited) significantly improves disease control and patients' quality of life.1,2



The study known as CLIMB, compared 12 weeks treatment with budesonide/formoterol (400/12 mcg one inhalation twice-daily) plus tiotropium (18 ?µg one inhalation once daily) vs. tiotropium alone plus placebo.


"Combined inhaled corticosteroid (ICS) and long-acting beta-agonist (LABA) therapy with budesonide/formoterol (Symbicort®) is indicated for COPD patients with a forced expiratory volume in 1 second (FEV1) < 50% predicted normal and a history of repeated exacerbations",3 explained Professor Tobias Welte, the international coordinating investigator of the CLIMB study. "While budesonide/formoterol combination is commonly used together with tiotropium for the management of patients with severe COPD, CLIMB is the first study to evaluate the therapeutic effect of combining budesonide/formoterol with tiotropium. The results of the study confirmed that this triple therapy regimen has a key role to play in the management of patients with COPD," he continued.


CLIMB showed that tiotropium plus budesonide/formoterol combination versus tiotropium alone:


- reduced the rate of severe exacerbations by 62% (p







Full results of the CLIMB study are due to be published later in 2009.


Notes


An estimated 3.7 million people in the UK have COPD; COPD is the 5th biggest killer in the UK; around 30,000 people in the UK die from COPD each year, which is more than from bowel cancer, breast cancer or prostate cancer.6



References


1. Welte T, et al. Budesonide/formoterol added to tiotropium improves the management of COPD patients. American Thoracic Society International Conference, San Diego, USA, 15-20 May 2009; Abst 953775.


2. Welte T, et al. Budesonide/formoterol added to tiotropium is well tolerated and reduces the risk of severe exacerbations in COPD patients. American Thoracic Society International Conference, San Diego, USA, 15-20 May 2009; Abst 953763.


3. Symbicort 400/12® Summary of Product Characteristics, December 2008.


4. Miravitlles M et al. Patient's perception of exacerbations of COPD - The PERCEIVE study. Respir Med 2007; 101: 453-60.


5. 'Unleash the life within...' a patient's perspective of living with Chronic Obstructive Pulmonary Disease (COPD) Survey. Sponsored by AstraZeneca UK Ltd.


6. British Lung Foundation. Invisible Lives. Chronic Obstructive Pulmonary Disease (COPD) - finding the missing millions, November 2007.


Source
AstraZeneca


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