Alpha-1-antitrypsin (AAT) is a member of the serine proteinase inhibitor (serpin) family of proteins with a broad spectrum of biological functions including inhibition of proteases, immune modulatory functions, and the transport of hormones.

Serial Peak Expiratory Flow measurement at work and home is a feasible, sensitive, and specific test for the diagnosis of occupational asthma. For a diagnosis of occupational asthma, it is important to establish a relationship objectively between the workplace exposure and asthma symptoms and signs. Physiologically, this can be achieved by monitoring airflow limitation in relation to occupational exposure(s). If there is an effect of a specific workplace exposure, airflow limitation should be more prominent on work days compared with days away from work (or days away from the causative agent). Airflow limitation can be measured by spirometry, with peak expiratory flow (PEF) and/or forced expiratory volume in 1 s(FEV1) being the most useful for observing changes in airway calibre. Other tests mentioned are less reliable and would not help in establishing a satisfactory diagnosis of occupational asthma.

Malignant mesothelioma is a type of cancer that occurs in the thin layer of tissue that covers the majority of the internal organs (mesothelium).
Malignant Mesothelioma (MM) is a rare but rapidly fatal and aggressive tumour of the pleura and peritoneum. Aetiology of all forms of mesothelioma is strongly associated with industrial pollutants, of which asbestos is the principal carcinogen.

Thoracoscopically guided biopsy should be performed if mesothelioma is suggested; the results are diagnostic in 98% of cases. No specific treatment has been found to be of benefit, except radiotherapy, which reduces seeding and invasion through percutaneous biopsy sites.

Median survival for patients with malignant mesothelioma is 11 months. It is almost always fatal.

The tumour has only invaded the visceral pleura and measures 3cm in the greatest dimension. Hence it is designated at T2. Ipsilateral peribronchial and/or hilar lymph node involvement would make it N1. There is no distal metastasis so M would be 0.

Acute exacerbations of chronic obstructive pulmonary disease (COPD) are immediately treated with inhaled beta2 agonists and inhaled anticholinergics, followed by antibiotics (if indicated) and systemic corticosteroids. Methylxanthine therapy may be considered in patients who do not respond to other bronchodilators.
High flow oxygen would worsen his symptoms. Usually titrated oxygen (88 to 92 %) is given in such patients to avoid the risk of hyperoxic hypercarbia in which increasing oxygen saturation in a chronic carbon dioxide retainer can inadvertently lead to respiratory acidosis and death.

Alpha-1 antitrypsin deficiency is an inherited disorder that may cause lung and liver disease. The signs and symptoms of the condition and the age at which they appear vary among individuals. This would be the most likely option as it is the only disease that can affect both liver and lung functions.
People with alpha-1 antitrypsin deficiency usually develop the first signs and symptoms of lung disease between ages 20 and 50. The earliest symptoms are shortness of breath following mild activity, reduced ability to exercise, and wheezing. Other signs and symptoms can include unintentional weight loss, recurring respiratory infections, fatigue, and rapid heartbeat upon standing. Affected individuals often develop emphysema. Characteristic features of emphysema include difficulty breathing, a hacking cough, and a barrel-shaped chest. Smoking or exposure to tobacco smoke accelerates the appearance of emphysema symptoms and damage to the lungs.
About 10 percent of infants with alpha-1 antitrypsin deficiency develop liver disease, which often causes yellowing of the skin and sclera (jaundice). Approximately 15 percent of adults with alpha-1 antitrypsin deficiency develop liver damage (cirrhosis) due to the formation of scar tissue in the liver. Signs of cirrhosis include a swollen abdomen, swollen feet or legs, and jaundice. Individuals with alpha-1 antitrypsin deficiency are also at risk of developing hepatocellular carcinoma.

Phrenic nerve palsy causing hemidiaphragm paralysis is a very uncommon feature of thoracic aortic aneurysm.

Thoracic aortic aneurysms are usually asymptomatic however chest pain is most commonly reported symptom. Left hemidiaphragm paralysis, because of left phrenic nerve palsy, is a very rare presentation of thoracic aortic aneurysm.
Thoracic aortic aneurysm may present atypical symptoms such as dysphagia due to compression of the oesophagus; hoarseness due to vocal cord paralysis or compression of the recurrent laryngeal nerve; superior vena cava syndrome due to compression of the superior vena cava; cough, dyspnoea or both due to tracheal compression; haemoptysis due to rupture of the aneurysm into a bronchus; and shock due to rupture of the aneurysm.
Common causes of phrenic nerve palsy include malignancy such as bronchogenic carcinoma, as well as mediastinal and neck tumours. Phrenic nerve palsy can also occur due to a penetrating injury or due to iatrogenic causes arising, for example, during cardiac surgery and central venous catheterization. Many cases or phrenic nerve palsy are idiopathic.

COPD is commonly associated with progressive hypoxemia. Oxygen administration reduces mortality rates in patients with advanced COPD because of the favourable effects on pulmonary hemodynamics.

Long-term oxygen therapy improves survival 2-fold or more in hypoxemic patients with COPD, according to 2 landmark trials, the British Medical Research Council (MRC) study and the US National Heart, Lung and Blood Institute’s Nocturnal Oxygen Therapy Trial (NOTT). Hypoxemia is defined as PaO2 (partial pressure of oxygen in arterial blood) of less than 55 mm Hg or oxygen saturation of less than 90%. Oxygen was used for 15-19 hours per day.

Therefore, specialists recommend long-term oxygen therapy for patients with a PaO2 of less than 55 mm Hg, a PaO2 of less than 59 mm Hg with evidence of polycythaemia, or cor pulmonale. Patients should be evaluated after 1-3 months after initiating therapy, because some patients may not require long-term oxygen.

In adult practice, biochemical analysis of pleural fluid plays an important part in the management of pleural effusions. Protein levels or Light’s criteria differentiate exudates from transudates, while infection is indicated by pleural acidosis associated with raised LDH and low glucose levels. In terms of treatment, the pH may even guide the need for tube drainage, suggested by pH <7.2 in an infected effusion, although the absolute protein values are of no value in determining the likelihood of spontaneous resolution or chest drain requirements. pH is therefore the most important factor.

Cystic fibrosis (CF) is a multisystemic, autosomal recessive disorder that predominantly affects infants, children, and young adults. CF is the most common life-limiting genetic disorder in whites, with an incidence of 1 case per 3200-3300 new-borns in the United States.

People with CF can have a variety of symptoms, including:
Very salty-tasting skin
Persistent coughing, at times with phlegm
Frequent lung infections including pneumonia or bronchitis
Wheezing or shortness of breath
Poor growth or weight gain in spite of a good appetite
Frequent greasy, bulky stools or difficulty with bowel movements
Male infertility

Signs of bronchiectasis include the tubular shadows; tram tracks, or horizontally oriented bronchi; and the signet-ring sign, which is a vertically oriented bronchus with a luminal airway diameter that is 1.5 times the diameter of the adjacent pulmonary arterial branch.

Bronchiectasis is characterized by parallel, thick, line markings radiating from hila (line tracks) in cylindrical bronchiectasis. Ring shadows represent dilated thick-wall bronchi seen in longitudinal section or on-end or dilated bronchi in varicose bronchiectasis.

Pseudomonas aeruginosa is the key bacterial agent of cystic fibrosis (CF) lung infections, and the most important pathogen in progressive and severe CF lung disease. This opportunistic pathogen can grow and proliferate in patients, and exposure can occur in hospitals and other healthcare settings.

Haemophilus influenzae is regularly involved in chronic lung infections and acute exacerbations of CF patients

Peak Expiratory Flow (PEF), also called Peak Expiratory Flow Rate (PEFR) is a person’s maximum speed of expiration, as measured with a peak flow meter. Measurement of PEFR requires some practise to correctly use a meter and the normal expected value depends on a patient’s gender, age and height.
It is classically reduced in obstructive lung disorders, such as Asthma, COPD or Cystic Fibrosis.

Community-acquired pneumonia (CAP) is one of the most common infectious diseases and is an important cause of mortality and morbidity worldwide. Typical bacterial pathogens that cause CAP include Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.
The CURB-65 is used as a means of deciding the action that is needed to be taken for that patient.
Score 3-5: Requires hospitalization with consideration as to whether they need to be in the intensive care unit

Recent studies have suggested that the use of a beta-lactam alone may be noninferior to a beta-lactam/macrolide combination or fluoroquinolone therapy in hospitalized patients.

Therapy in ICU patients includes the following:
– Beta-lactam (ceftriaxone, cefotaxime, or ampicillin/sulbactam) plus either a macrolide or respiratory fluoroquinolone
– For patients with penicillin allergy, a respiratory fluoroquinolone and aztreonam

Therefore the appropriate treatment would be Cefotaxime and erythromycin.

A single dose of intravenous magnesium sulphate is safe and may improve lung function and reduce intubation rates in patients with acute severe asthma. Intravenous magnesium sulphate may also reduce hospital admissions in adults with acute asthma who have had little or no response to standard treatment.

Consider giving a single dose of intravenous magnesium sulphate to patients with acute severe asthma (PEF <50% best or predicted) who have not had a good initial response to inhaled bronchodilator therapy. Magnesium sulphate (1.2–2 g IV infusion over 20 minutes) should only be used following consultation with senior medical staff.

CURB Pneumonia Severity Score estimates the mortality of community-acquired pneumonia to help determine inpatient vs. outpatient treatment.
Select Criteria:
Confusion (abbreviated Mental Test Score <=8) (1 point)
Urea (BUN > 19 mg/dL or 7 mmol/L) (1 point)
Respiratory Rate > 30 per minute (1 point)
Blood Pressure: diastolic < 60 or systolic < 90 mmHg (1 point) The CURB-65 scores range from 0 to 5. Clinical management decisions can be made based on the score:
Score Risk Disposition
0 or 1 – 1.5% mortality – Outpatient care
2 – 9.2% mortality – Inpatient vs. observation admission
≥ 3 – 22% mortality – Inpatient admission with consideration for ICU admission with score of 4 or 5

The NICE 2017 guidelines state that in patients who are uncontrolled with a SABA (Salbutamol) and ICS (Inhaled corticosteroid e.g. Beclomethasone), a leukotriene receptor antagonist (LTRA) should be added.
If asthma is uncontrolled in adults (aged 17 and over) on a low dose of ICS as maintenance therapy, offer a leukotriene receptor antagonist (LTRA) in addition to the ICS and review the response to treatment in 4 to 8 weeks.

This recommendation is also stated in NICE 2019 guidelines.

Caplan’s syndrome is defined as the association between silicosis and rheumatoid arthritis (RA). It is rare and usually diagnosed in an advanced stage of RA. It generally affects patients with a prolonged exposure to silica.

Caplan’s syndrome presents with rheumatoid lung nodules and pneumoconiosis. Originally described in coal miners with progressive massive fibrosis, it may also occur in asbestosis, silicosis and other pneumoconiosis. Chest radiology shows multiple, round, well defined nodules, usually 0.5 – 2.0 cm in diameter, which may cavitate and resemble tuberculosis.

Severe acute respiratory syndrome (SARS) is a viral respiratory illness caused by a coronavirus called SARS-associated coronavirus (SARS-CoV). SARS was first reported in Asia in February 2003.
In general, SARS begins with a high fever (temperature greater than 38.0°C). Other symptoms may include headache, an overall feeling of discomfort, and body aches. Some people also have mild respiratory symptoms at the outset. About 10 to 20 percent of patients have diarrhoea. After 2 to 7 days, SARS patients may develop a dry cough. Most patients develop pneumonia. 

Salbutamol stimulates beta-2 adrenergic receptors, which are the predominant receptors in bronchial smooth muscle (beta-2 receptors are also present in the heart in a concentration between 10% and 50%).

Stimulation of beta-2 receptors leads to the activation of enzyme adenyl cyclase that forms cyclic AMP (adenosine-mono-phosphate) from ATP (adenosine-tri-phosphate). This increase of cyclic AMP relaxes bronchial smooth muscle and decrease airway resistance by lowering intracellular ionic calcium concentrations. Salbutamol relaxes the smooth muscles of airways, from trachea to terminal bronchioles.

Increased cyclic AMP concentrations also inhibits the release of bronchoconstrictor mediators such as histamine and leukotriene from the mast cells in the airway.

Assess the need for oxygen therapy in people with:
– very severe airflow obstruction (FEV1 below 30% predicted)
– cyanosis (blue tint to skin)
– polycythaemia
– peripheral oedema (swelling)
– a raised jugular venous pressure
– oxygen saturations of 92% or less breathing air.

Also consider assessment for people with severe airflow obstruction (FEV1 30–49% predicted).

Consider long-term oxygen therapy for people with COPD who do not smoke and who:
have a partial pressure of oxygen in arterial blood (PaO2) below 7.3 kPa when stable or have a PaO2 above 7.3 and below 8 kPa when stable, if they also have 1 or more of the following:
– secondary polycythaemia
– peripheral oedema
– pulmonary hypertension.

Bronchopneumonia presents as a patchy consolidation involving one or more lobes, usually the dependent lung zones, a pattern attributable to aspiration of oropharyngeal contents.

Symptoms of bronchopneumonia may be like other types of pneumonia. This condition often begins with flu-like symptoms that can become more severe over a few days. The symptoms include:
– fever
– a cough that brings up mucus
– shortness of breath
– chest pain
– rapid breathing
– sweating
– chills
– headaches
– muscle aches
– pleurisy, or chest pain that results from inflammation due to excessive coughing
– fatigue
– confusion or delirium, especially in older people

There are several factors that can increase your risk of developing bronchopneumonia. These include:
– Age: People who are 65 years of age or older, and children who are 2 years or younger, have a higher risk for developing bronchopneumonia and complications from the condition.
– Environmental: People who work in, or often visit, hospital or nursing home facilities have a higher risk for developing bronchopneumonia.
– Lifestyle: Smoking, poor nutrition, and a history of heavy alcohol use can increase your risk for bronchopneumonia.
– Medical conditions: Having certain medical conditions can increase your risk for developing this type of pneumonia. These include: chronic lung disease, such as asthma or chronic obstructive pulmonary disease (COPD), HIV/AIDS, having a weakened immune system due to chemotherapy or the use of immunosuppressive drugs.

Primary spontaneous pneumothorax is an abnormal accumulation of air in the space between the lungs and the chest cavity (called the pleural space) that can result in the partial or complete collapse of a lung. This type of pneumothorax is described as primary because it occurs in the absence of lung disease such as emphysema. Spontaneous means the pneumothorax was not caused by an injury such as a rib fracture. Primary spontaneous pneumothorax is likely due to the formation of small sacs of air (blebs) in lung tissue that rupture, causing air to leak into the pleural space. Air in the pleural space creates pressure on the lung and can lead to its collapse. A person with this condition may feel chest pain on the side of the collapsed lung and shortness of breath. Patients are typically aged 18-40 years, tall, thin, and, often, are smokers.

In small pneumothoraxes with minimal symptoms, no active treatment is required. These patients can be safely discharged with early outpatient review and should be given written advice to return if breathlessness worsens. Patients who have been discharged without intervention should be advised that air travel should be avoided until a radiograph has confirmed resolution of the pneumothorax.

Small cell lung cancer (SCLC) is characterized by rapid growth and early dissemination. Prompt initiation of treatment is important.

Patients with clinical stage Ia (T1N0) after standard staging evaluation may be considered for surgical resection, but combined treatment with chemotherapy and radiation therapy is the standard of care. Radiation therapy is often added at the second cycle of chemotherapy.

Historically, patients undergoing surgery for small cell lung cancer (SCLC) had a dismal prognosis. However, more recent data suggest that patients with true stage I SCLC may benefit from surgical resection.

Common sites of hematogenous metastases include the brain, bones, liver, adrenal glands, and bone marrow. The symptoms depend upon the site of spread.

The right and left lung anatomy are similar but asymmetrical. The right lung consists of three lobes: right upper lobe (RUL), right middle lobe (RML), and right lower lobe (RLL). The left lung consists of two lobes: right upper lobe (RUL) and right lower lobe (RLL). The right lobe is divided by an oblique and horizontal fissure, where the horizontal fissure divides the upper and middle lobe, and the oblique fissure divides the middle and lower lobes. In the left lobe there is only an oblique fissure that separates the upper and lower lobe.

The lobes further divide into segments which are associated with specific segmental bronchi. Segmental bronchi are the third-order branches off the second-order branches (lobar bronchi) that come off the main bronchus.

The right lung consists of ten segments. There are three segments in the RUL (apical, anterior and posterior), two in the RML (medial and lateral), and five in the RLL (superior, medial, anterior, lateral, and posterior). The oblique fissure separates the RUL from the RML, and the horizontal fissure separates the RLL from the RML and RUL.

There are eight to nine segments on the left depending on the division of the lobe. In general, there are four segments in the left upper lobe (anterior, apicoposterior, inferior and superior lingula) and four or five in the left lower lobe (lateral, anteromedial, superior and posterior). The medium sized airways offer the maximum airway resistance, not smaller ones.

If a pleural effusion is present, a diagnostic thoracentesis may be performed and analysed for pH, lactate dehydrogenase, glucose levels, specific gravity, and cell count with differential. Pleural fluid may also be sent for Gram stain, culture, and sensitivity. Acid-fast bacillus testing may also be considered and the fluid may be sent for cytology if cancer is suspected.

The following findings are suggestive of an empyema or parapneumonic effusion that will likely need a chest tube or pigtail catheter for complete resolution:
-Grossly purulent pleural fluid
-pH level less than 7.2
-WBC count greater than 50,000 cells/µL (or polymorphonuclear leukocyte count of 1,000 IU/dL)
-Glucose level less than 60 mg/dL
-Lactate dehydrogenase level greater than 1,000 IU/mL
-Positive pleural fluid culture

The most often used golden criteria for empyema are pleural effusion with macroscopic presence of pus, a positive Gram stain or culture of pleural fluid, or a pleural fluid pH under 7.2 with normal peripheral blood ph.

Sarcoidosis is an inflammatory disease that affects one or more organs but most commonly affects the lungs and lymph glands. The inflammation may change the normal structure and possibly the function of the affected organ(s).
The presentation in sarcoidosis varies with the extent and severity of organ involvement, as follows:
Asymptomatic (incidentally detected on chest imaging): Approximately 5% of cases.
Systemic complaints (fever, anorexia): 45% of cases
Pulmonary complaints (dyspnoea on exertion, cough, chest pain, and haemoptysis [rare]): 50% of cases

Löfgren syndrome (fever, bilateral hilar lymphadenopathy, and polyarthralgias): Common in Scandinavian patients, but uncommon in African-American and Japanese patients.

Dermatologic manifestations may include the following:
– Erythema nodosum
– A lower-extremity panniculitis with painful, erythematous nodules (often with Löfgren syndrome)
– Lupus pernio (the most specific associated cutaneous lesion)
– Violaceous rash on the cheeks or nose (common)
– Maculopapular plaques (uncommon)

Staging of sarcoidosis is as follows:
Stage 0: Normal chest radiographic findings
Stage I: Bilateral hilar lymphadenopathy
Stage II: Bilateral hilar lymphadenopathy and infiltrates
Stage III: Infiltrates alone
Stage IV: Fibrosis

Nonsteroidal anti-inflammatory drugs (NSAIDs) are indicated for the treatment of arthralgias and other rheumatic complaints. Patients with stage I sarcoidosis often require only occasional treatment with NSAIDs.

Treatment in patients with pulmonary involvement is as follows:
Asymptomatic patients may not require treatment
In patients with minimal symptoms, serial re-evaluation is prudent
Treatment is indicated for patients with significant respiratory symptoms
Corticosteroids can produce small improvements in the functional vital capacity and in the radiographic appearance in patients with more severe stage II and III disease.

This patient has Stage 1 Sarcoidosis so observation is the most appropriate action.

Pulmonary alveolar proteinosis (PAP) is a lung condition that is caused by a build-up of proteins and other substances in the alveoli. The alveoli are the part of the lungs that contain air. PAP has the following symptoms:
Shortness of breath, also called dyspnoea
Chest pain or tightness
Fever
Weight loss
Cough (sometimes, but not always)
Low levels of oxygen in the blood
Nail clubbing (abnormal growth of toenails or fingernails)

Serologic studies are generally not useful for PAP. Flexible bronchoscopy with bronchoalveolar lavage (BAL) remains the criterion standard. Elevated levels of the proteins SP-A and SP-D in serum and BAL fluid may be useful. Elevated titer of neutralizing autoantibody against GM-CSF (immunoglobulin G [IgG] isotype) in serum and BAL fluid may be useful. Recent studies have proposed that deficiency of GM-CSF causes pulmonary alveolar proteinosis (PAP); all patients studied had the antibody to GM-CSF. Serum lactate dehydrogenase (LDH) level is usually elevated, but this finding is nonspecific.

High-resolution computed tomography (HRCT) scan of the chest demonstrates areas of patchy ground-glass opacification with smooth interlobular septal thickening and intralobular interstitial thickening, which produces a polygonal pattern referred to as crazy paving.

Light microscopy of the lung parenchymal tissue shows alveoli filled with a granular PAS base-reactive and diastase-resistant eosinophilic material.

Allergic bronchopulmonary aspergillosis (ABPA) is a form of lung disease that occurs in some people who are allergic to Aspergillus. With ABPA, this allergic reaction causes the immune system to overreact to Aspergillus leading to lung inflammation. ABPA causes bronchospasm (tightening of airway muscles) and mucus build-up resulting in coughing, breathing difficulty and airway obstruction.

Blood tests are used to look for signs of an allergic reaction. This includes evaluating your immunoglobulin E (IgE) level. This level is increased with any type of allergy. Many people with asthma have higher than normal IgE levels. In ABPA however, the IgE level is extremely high (more than 1000 ng/ml or 417 IU/ml). In addition to total IgE, all patients with ABPA have high levels of IgE that is specific to Aspergillus. A blood test can be done to measure specific IgE to Aspergillus. A blood or skin test for IgE antibodies to Aspergillus can be done to see if a person is sensitized (allergic) to this fungus. If these skin tests are negative (i.e. does not show a skin reaction) to Aspergillus fumigatus, the person usually does not have ABPA.
Therefore, there should be no change in medication since this patient does not have ABPA.

Postmenopausal oestrogen therapy and hormone therapy are associated with an increased risk of thromboembolism. The relative risk seems to be even greater if the treated population has pre-existing risk factors for thromboembolism, such as obesity, immobilization, and fracture. Cor pulmonale can occur secondary to small recurrent pulmonary embolisms. Pneumonias and bronchiectasis usually present with purulent sputum, and in case of carcinoma there may be other associated symptoms like weight loss, etc.

The Stages of COPD:
Mild COPD or Stage 1—Mild COPD with a FEV1 about 80 percent or more of normal.
Moderate COPD or Stage 2—Moderate COPD with a FEV1 between 50 and 80 percent of normal.
Severe COPD or Stage 3—Severe emphysema with a FEV1 between 30 and 50 percent of normal.
Very Severe COPD or Stage 4—Very severe or End-Stage COPD with a lower FEV1 than Stage 3, or people with low blood oxygen levels and a Stage 3 FEV1.

This patient has a FEV1 percent of 40 which falls within the stage 2 or moderate COP

The Stages of COPD:
Mild COPD or Stage 1—Mild COPD with a FEV1 about 80 percent or more of normal.
Moderate COPD or Stage 2—Moderate COPD with a FEV1 between 50 and 80 percent of normal.
Severe COPD or Stage 3—Severe emphysema with a FEV1 between 30 and 50 percent of normal.
Very Severe COPD or Stage 4—Very severe or End-Stage COPD with a lower FEV1 than Stage 3, or people with low blood oxygen levels and a Stage 3 FEV1.

This patient has a FEV1 percent of 37 which falls within the stage 3 or severe COPD.
During stage 3 COPD, you will likely experience significant lung function impairment. Many patients will experience an increase in COPD flare-ups or exacerbations. For some people, the increase in flare-ups means they could need to be hospitalized at times as well.

Inhaled corticosteroid (ICS) use in combination with long-acting β2-agonists (LABAs) was shown to provide improved reductions in exacerbations, lung function, and health status. ICS-LABA combination therapy is currently recommended for patients with a history of exacerbations despite treatment with long-acting bronchodilators alone. The presence of eosinophilic bronchial inflammation, detected by high blood eosinophil levels or a history of asthma or asthma–COPD overlap, may define a population of patients in whom ICSs may be of particular benefit.

The Towards a Revolution in COPD Health (TORCH) trial was a pivotal, double-blind, placebo-controlled, randomized study comparing salmeterol plus fluticasone propionate (50 and 500 µg, respectively, taken twice daily) with each component alone and placebo over 3 years.26 Patients with COPD were enrolled if they had at least a 10-pack-year smoking history, FEV1 <60% predicted, and an FEV1:FVC ratio ≤0.70.26 Among 6,184 randomized patients, the risk of death was reduced by 17.5% with the ICS-LABA combination vs placebo (P=0.052). ICS-LABA significantly reduced the rate of exacerbations by 25% compared with placebo (P<0.001) and improved health status and FEV1 compared with either component alone or placebo.