Diagnosis and Management of Chronic Obstructive Pulmonary Disease

Abstract

This chapter describes the chronic obstructive pulmonary diseases (COPD) its diagnosis, management and recent advances. Because it is third leading cause of death in world. It must be given more attention and discussion. COPD was broadly divided into Stable COPD, Infective COPD and Exacerbation COPD all of which have different management criteria. COPD is frequently misdiagnosed with other chronic respiratory diseases but the Global initiative for Chronic Obstructive Lung Disease score and the COPD assessment test score help to assess the disease. It is preventable and treatable diseases so the multidisciplinary approach should be followed so that the care of the patient is done in all the dimensions. Pulmonary rehabilitation is one of the advances and it shows major benefits for COPD patients.

1. Introduction

In the recent definition given by Global initiative for Chronic Obstructive Lung Disease (GOLD), chronic obstructive pulmonary diseases (COPD) is defined as common, preventable and treatable diseases that is characterized by persistent respiratory symptoms and airflow limitations that arise from airway and/or alveolar abnormalities usually caused by significant exposure to noxious particle or gases. In high income countries the main risk factor of exposure is smoking and in low income countries, occupational exposure. COPD is a heterogeneous disease, but has a uniform GOLD definition in terms of lung function, exacerbation history and symptoms. The center hallmark of COPD is inflammation which plays a significant role in persistent changes in different sections of lungs. Another main risk factor for COPD is genetic predisposition and toxic exposure. COPD is thus a disease in which genetic abnormalities in combination of with the type and duration of exposures determine the clinical phenotype [1].

In COPD, chronic inflammations take place that lead to many structural and functional changes such as narrowing of the small airways and demolition of lung parenchyma, which results in loss of elastic recoil. These changes decrease the ability of the airway to open during expiration [2]. The main characteristic symptoms of the disease is airflow limitations and dysfunction in mucociliary function [3]. Several structural abnormalities present in COPD are shown in Figure 1 Emphysema is defined as “destruction of gas exchange process on the surface of lung alveoli”. Chronic bronchitis is an increase in the production of cough and sputum.

Figure 1.

COPD phenotypes which shows the structure of normal lungs and the abnormalities in COPD.

2. Prevalence

COPD is a highly prevalent disease, with over 250 million case worldwide presenting with severe chronic lung disease. Previously it was the fourth major cause of death globally, but in 2020 it was third. Recently it is observed that the prevalence of the disease is directly proportional to the consumption of tobacco smoking. The major risk factors for the prevalence of disease in many countries are occupational environment, pollution, and consumption of other biomass fuels. Therefore, it is predicted that the prevalence of the disease is increasing in the upcoming years due to aging of the population and exposure to these risk factors [4, 5].

3. Symptoms

The symptoms of COPD according to World Health Organization are shortness of breath, persistent cough, chest infection, wheezing, and weight loss and chest tightness.

4. Risk factors

4.1 Genetic factors

A genetic risk factor is a deficiency of alpha-1 antitrypsin (AATD). This deficiency is present in small portion of the world population, and it demonstrate the relationship between the genes and environmental factors that make an individual susceptible to COPD. Evidence suggests that a familial risk of airflow limitation is present in people who smoke and are sibling of patients with severe COPD [6].

4.2 Age and sex

Aging is associated with structural changes in parenchyma and in airways that may be associated with COPD. Most studies in the past have shown COPD is more prevalent in men, but recent studies show almost equal prevalence in men and women because of the consumption of tobacco smoking [7]. The prevalence of nonsmoking-related COPD is higher among women than among men. In the international BOLD study, among 4291 nonsmokers aged >40 years, 6.6% had COPD stage I and 5.6% had COPD stage II or higher [8].

4.3 Lung growth and development

The growth and development take place over extended periods, during the period of gestation, throughout childhood and into adolescence. Spirometer tests can reveal the increased risk of COPD and show that any factor that affects the growth of lung increases the risk of developing COPD. Lung infection during childhood is one of the contributing factors [9].

4.4 Socioeconomic factors

Lower socioeconomic status and poverty are associated with airflow obstruction, leading to increased risk of COPD. Reasons for the association include exposure of air pollutants, indoor and outdoor, infections and poor nutrition [9].

4.5 Exposure to particles

Cigarette smoking is the most common risk factor of COPD across the world. Compared to non-smokers, smokers have a greater chance of developing functional abnormality of lungs like decline in FEV1 values and other respiratory symptoms. Environmental tobacco smoke (ETS), commonly known as passive expose to cigarette smoke may also promote respiratory symptoms leading to COPD. When the smoking continues during pregnancy it also affects the growth and development of lungs of fetus. Occupational exposures to chemical agents, organic and inorganic, fumes, and other irritants are the risk factors of COPD. The high level of indoor pollution used for cooking in many houses such as that released from stoves that use wood, or animal dung typically increased the burden [10]. Among all smokers, 17.8% (1663/9169) had COPD (including incident and prevalent cases), whereas in never smokers the prevalence of COPD was 6.4% (318/4997). In men, 17.3% (n = 1042/6024) were never smokers, compared to 46.0% (n = 3955/8595) never smoking women. The proportion of COPD female cases without a smoking history was 27.2% (236/867), while the proportion of never smokers among COPD male cases was 7.3% (82/1126) [11].

4.6 Infections

Children who have a history of respiratory infections have reduced lung functional volumes and increased symptoms in their early adulthood. The infections play a susceptible role in exacerbation of COPD but development is not clear [12].

4.7 Chronic bronchitis

Chronic bronchitis was not directly associated with decline in lung functions. However, evidence shows association with hyper secretion and the FEV1 value of adults who smoke. The presence of diseases is associated with developing COPD [13].

5. Clinical manifestation

As shown in Figure 2 the etiology of COPD includes smoking, pollutants, and other host factors, which leads to pathological abnormalities like emphysema and airway abnormality. These pathological abnormalities lead to increase in symptoms of COPD like airflow limitation, increase in secretion, and dyspnea [14].

Figure 2.

The etiology and clinical manifestation of chronic obstructive pulmonary diseases.

6. Pathophysiology

Chronic obstructive pulmonary disease is characterized by many morphological and cellular changes that happen in the airways and in the lung parenchyma. These changes cause progressive airflow limitation by abnormal inflammatory reaction and poorly reversible airflow obstruction in the lungs. There may be inflammation in the lungs of cigarette smokers, but some of them have abnormal response of that agent that leads to COPD. As the response increases it leads to hypersecretion of mucous, called chronic bronchitis, and tissue destruction called emphysema and fibrosis.

As illustrated in Figure 3 cigarette smoke and biomass fuel trigger the pathogenic changes such as inflammatory mediators, sub epithelial infiltration, CD-8 cells, CD-4 lymphocytes, macrophages and oxidative stress, which leads to destruction of alveoli, destruction of alveolar attachments, airway narrowing, goblet cell hyperplasia and peri-bronchial fibrosis. These pathologies are manifested by symptoms like dyspnoea, cough, and mucus hypersecretion.

Figure 3.

Pathogenesis of COPD.

Even after smoking cessations severity of the diseases can increase because many exacerbating structural and inflammatory changes have already taken place. Apart from inflammation, other processes take an active part in pathogenesis of COPD like imbalance between the proteases and antiproteases and oxidants and antioxidants (oxidative stress) in the lungs [15].

6.1 Inflammatory cells

Airflow obstruction in COPD is due to the increase in inflammatory cells such as neutrophils, T-lymphocytes and macrophages. Inflammatory cells release a variety of mediators and cytokines that promote progression of the disease.

6.2 Inflammatory mediators

Inflammatory mediators in COPD like macrophages and neutrophils produce Leukotriene B and T-cell chemoattractant. These agents amplify the pro-inflammatory response, and include CXC chemokines interleukin 8, and oncogene α, which is produced by epithelial cells.

6.2.1 Protease and antiprotease imbalance

An imbalance can occur between activation and production of proteases and reduction or inactivation of antiproteases. During cigarette smoke, the inflammation response produces an oxidative stress which releases a combination of proteases and in actives the antiproteases. Two main proteases are neutrophils, such as cathepsin G and proteases 3, and macrophages, such as cathepsins E, L, and S. Antiprotease includes secretory leucoprotease inhibitor, and tissue inhibitors of metalloproteases.

When an imbalance occurs between the proteases and antiproteases, alveolar wall destruction in emphysema and proteases causes mucous release. Increased oxidant from smoke releases chemostatic factors in turn directly affecting the mucous secretion and injury to alveolar walls.

As we discuss above, the pathogenic changes that are present in COPD causes many physiological abnormalities like air flow obstruction, mucous hypersecretion, pulmonary hypertension and ciliary dysfunction.

6.2.2 Airflow obstruction and hyperinflation or air trapping

The main factors of obstruction firstly occur in small airways of diameter less than 2 mm, because narrowing and inflammation flow into the small airways. Other factors contributing to airflow obstruction are loss of alveolar support and lung elastic recoil. The airway obstruction takes place due to increased trapping of air during the expiration phase of breathing that in turn hyper inflate at resting position and during exercise the trapping turns into dynamic hyperinflation. This process decreases the inspiratory capacity and lastly functional residual capacity results in breathlessness. The standard way of measuring the airflow obstruction to is by spirometry.

6.2.3 Mucous hypersecretion and ciliary dysfunction

Chronic productive cough is due to hypersecretion of mucous. The main characteristic of chronic bronchitis is mucous hypersecretion but not airflow obstruction. The irritation in the lung is by noxious particles, which result in hypersecretion due to increased size of sub mucosal glands, squamous metaplasia, and goblet cells.

6.2.4 Pulmonary hypertension

Pulmonary hypertension develops during progression of the diseases from abnormalities in the process of gas exchange. The factors leading to pulmonary hypertension are pulmonary arterial constriction and dysfunction of endothelium, and pulmonary capillary bed. In pulmonary arterioles, structural changes lead to right ventricular hypertrophy, pulmonary hypertension and cor pulmonale.

6.2.5 Gas exchange abnormality

Anatomical changes in COPD disturb the ventilation perfusion ratio—the main cause of gas exchange abnormalities. This disturbance is seen when progression of the diseases take place.

Despite significant progress over the last decade, COPD management has seen relatively few advancements. The existing medications do not considerably slow down the ongoing decline in airway function. Consequently, the main focus of treatment lies in enhancing lung function through bronchodilators and adopting healthier lifestyle practices. Since the airway obstruction in COPD is generally irreversible and current treatments do not change the course of the disease, the benefits of existing drug therapies are somewhat limited for patients.

7. Diagnosis and characterization

7.1 The GOLD score

The GOLD report categorizes COPD into four stages as follows,

7.1.1 Stage I: mild

FEV1 ≥ 80% predicted: the FEV1 value is greater than or equal to 80% of the predicted value for a person of the same age, sex, and height.

Symptoms: Mild airflow limitation with occasional symptoms such as chronic cough and sputum production. Shortness of breath may not be noticeable during normal activities.

7.1.2 Stage II: moderate

FEV1 50–79% predicted: The FEV1 value is between 50% and 79% of the predicted value.

Symptoms: Increased breathlessness during physical activities. Cough and sputum production are more noticeable, and exacerbation (worsening of symptoms) can occur.

7.1.3 Stage III: severe

FEV1 30–49% predicted: The FEV1 value is between 30% and 49% of the predicted value.

Symptoms: Further increase in breathlessness, reduced exercise tolerance, and more frequent exacerbations. Quality of life is significantly affected.

7.1.4 Stage IV: very severe

FEV1 < 30% predicted: The FEV1 value is less than 30% of the predicted value or FEV1 is <50% predicted with chronic respiratory failure (low oxygen levels).

Symptoms: Severe airflow limitation, extreme breathlessness even during minimal physical activity or at rest. Exacerbations, respiratory failure, and decreased quality of life are common.

7.2 The MMRC scale

In parallel with the GOLD score, the Modified Medical Research Council Dyspnea Scale is a tool used to assess the severity of breathlessness or dyspnea in patients with conditions such as COPD. It helps to understand the impact of breathlessness on a person’s daily life and activities.

The scale provides a simple way for patients to describe their level of breathlessness.

The MMRC scale consists of five levels, each corresponding to a different degree of breathlessness:

1. Grade 0: Breathlessness only with strenuous exercise.

2. Grade 1: Breathless when walking up a slight hill or walking at a normal pace on level ground.

3. Grade 2: Walks slower than people of the same age on level ground because of breathlessness, or needs to stop for breath when walking at own pace on level ground.

4. Grade 3: Stops for breath after walking about 100 meters or after a few minutes on level ground.

5. Grade 4: Too breathless to leave the house or breathless when dressing or undressing.

This scale helps to understand the impact of COPD on a patient’s daily activities and quality of life. It’s used in conjunction with other assessments, such as lung function tests and symptom evaluations, to guide treatment decisions and monitor disease progression.

7.3 Spirometry

Spirometry is a crucial diagnostic test used to assess lung function and diagnose conditions like COPD. Spirometry findings in COPD typically show characteristic patterns associated with the disease:

1. FEV1:

   • In COPD, FEV1 is reduced due to airway obstruction and reduced lung elasticity.

   • A lower FEV1 value indicates more severe airflow limitation.

2. FVC:

   • FVC can also be reduced in COPD due to lung hyperinflation and air trapping.

3. FEV1/FVC ratio:

   • In healthy individuals, this ratio is typically high (around 80–90%) because they can exhale a large amount of air quickly.

   • In COPD, this ratio is reduced due to the airflow obstruction. It’s a hallmark finding of the disease.

Based on the spirometry results, COPD can be classified into different stages according to the GOLD staging system:

• Stage I: Mild COPD—FEV1/FVC < 70% and FEV1 ≥ 80% predicted.

• Stage II: Moderate COPD—FEV1/FVC < 70% and 50% ≤ FEV1 < 80% predicted.

• Stage III: Severe COPD—FEV1/FVC < 70% and 30% ≤ FEV1 < 50% predicted.

• Stage IV: Very Severe COPD—FEV1/FVC < 70% and FEV1 < 30% predicted or FEV1 < 50% predicted with respiratory failure.

Spirometry findings, along with symptoms, exacerbation history, and other assessments, helps to guide treatment decisions and disease management strategies for individuals with COPD.

7.4 The CAT score

The COPD Assessment Test (CAT) is a questionnaire used to assess the impact of COPD on a patient’s health status and daily life. The CAT questionnaire consists of eight items that cover different aspects of COPD-related symptoms and their impact. The total CAT score ranges from 0 to 40, with higher scores indicating a greater impact of COPD on the patient’s quality of life. The scores are often categorized into four groups (A, B, C, and D) to guide treatment decisions and management strategies. These categories are determined by the total CAT score and the number of exacerbations experienced by the patient in the previous year.

Group A: low symptoms, low risk (CAT score < 10).

• Patients in this group have a relatively low impact of COPD symptoms on their quality of life.

• They are considered to have fewer symptoms and a lower risk of exacerbations.

• Treatment may focus on relieving symptoms, improving exercise tolerance, and promoting overall well-being.

Group B: high symptoms, low risk (CAT score ≥ 10).

• Patients in this group have a higher impact of COPD symptoms on their quality of life.

• They are still considered to have a lower risk of exacerbations.

• Treatment may involve bronchodilators and other medications to manage symptoms and improve lung function.

Group C: low symptoms, high risk (CAT score < 10).

• Patients in this group have fewer symptoms, but their risk of exacerbations is higher due to factors such as frequent exacerbations in the past.

• Treatment may focus on reducing the risk of exacerbations through interventions like long-acting bronchodilators, inhaled corticosteroids, or other appropriate medications.

Group D: high symptoms, high risk (CAT score ≥ 10).

• Patients in this group experience a significant impact of COPD symptoms on their quality of life and have a higher risk of exacerbations.

• Treatment may involve a combination of bronchodilators, inhaled corticosteroids, and other medications to manage symptoms and reduce the risk of exacerbations.

The CAT score categories help healthcare providers tailor treatment plans to individual patient needs, with the goal of improving symptoms, quality of life, and overall disease management.

7.5 Chest X-ray

Chest X-rays can exhibit the following indicators of COPD:

1. Hyper inflated lungs with flattened diaphragm.

2. Increased lung markings.

3. Narrowed heart shadow or flattening of the heart.

4. Bullae within the lung tissue.

5. Increased retrosternal airspace.

8. Risk factors and prevention strategies in COPD

In this section, we delve into the intricate web of risk factors associated with (COPD) and explore strategies to prevent its development. Understanding the interplay between genetic predisposition and environmental influences is crucial in deciphering the roots of this complex disease.

8.1 Environmental risk factors

We start by dissecting the crucial role of environmental factors. In developed nations, the chief contributor to COPD is cigarette smoking, whereas in developing countries, exposure to environmental pollutants like particulates from cooking with biomass fuels in confined spaces emerges as a significant trigger. Surprisingly, even among non-smokers, COPD accounts for a substantial portion of cases, suggesting diverse causes. Some instances stem from asthma evolving into COPD, identified by early onset and a history of variable symptoms. In countries like India, where biomass fuel exposure is prevalent, particularly among women, it becomes a major COPD risk factor.

Air pollution, certain workplace chemicals, such as cadmium, and passive smoking also amplify risk. The exact role of airway hyper-responsiveness and allergy in COPD remains uncertain. Nutrition, particularly during fetal life, plays a role—low birth weight leads to smaller lungs and earlier lung function decline. Early chest infections and latent virus infections like adenovirus might also influence COPD development. The connection between COPD and tuberculosis adds complexity to the picture [16].

8.2 Preventing environmental risks

A cornerstone of COPD prevention lies in avoiding environmental risks. Foremost attention is directed towards curbing smoking.

8.3 Smoking cessation

The act of quitting smoking yields the most rewarding outcomes. It not only slows down lung function decline but also curtails exacerbations and cardiovascular risks. Stopping smoking is most effective early in the disease and slightly less so as COPD advances.

Nicotine addiction complicates quitting, which should be seen as a remedy for drug addiction. Abrupt cessation often trumps gradual reduction, although, even after intensive programs, 75% of smokers remain at it a year later. Various methods aid in cessation: psychological counseling, group therapy, and nicotine replacement therapy (available as gum, patches, nasal spray, and inhalers). Bupropion, an unconventional antidepressant, and varenicline, a partial nicotinic agonist, show promise in aiding cessation [17].

8.4 Mitigating biomass fuel exposure

For those in developing countries, tackling COPD risk from biomass fuel exposure becomes pivotal. Alternative fuels like Liquefied Petroleum Gas (LPG) and natural gas, as well as improved stoves, improved ventilation, and cooking outdoors, offer preventive measures [18].

8.5 Genetic factors

Genetic predisposition’s role comes to the forefront. Lung function monitoring in smokers reveals that a fraction of patients develops significant airflow obstruction due to accelerated lung function decline—genetics likely play a role. Patients with alpha 1-antitrypsin deficiency manifest genetic susceptibility to COPD. Yet, these cases are relatively rare. Genetic associations with other forms of COPD are still being explored, but few conclusive links have emerged [19].

8.6 Genetic research

Advances in genetic research reveal intriguing insights. Polymorphisms in genes related to nicotine addiction and nicotinic receptors surface as potential susceptibility markers. Techniques like gene chips, proteomics, and gene expression profiling are being harnessed to unravel the molecular nuances behind COPD development [20].

In this chapter, we navigate the multifaceted landscape of COPD risk factors, drawing attention to genetic influences, environmental triggers, and innovative prevention measures. Understanding this interplay enhances our ability to mitigate the onset and progression of this debilitating condition [21].

9. Treatment

9.1 Bronchodilators

9.1.1 Bronchodilator effect

Bronchodilators form the linchpin of COPD treatment, even though their effect on lung function is relatively modest in the context of COPD compared to asthma. Typically, they bring about around a 5% enhancement in FEV1, with some patients experiencing more substantial responses. Yet, their significance extends beyond this lung function improvement.

9.1.2 Beyond lung function

Bronchodilators have broader implications for COPD patients. They can alleviate shortness of breath and enhance exercise capacity, even when spirometry results show limited improvement. By reducing lung volumes, they mitigate hyperinflation, a condition marked by trapped air. This reduction in trapped air can lead to improved breathing during exercise and day-to-day activities. Additionally, bronchodilators might aid in reducing fatigue in respiratory muscles (although this is debated) and enhancing the clearing of mucus from the airways.

9.1.3 Choices in bronchodilators

Selecting the right bronchodilator hinges on patient preferences and cost considerations. Options encompass both short and long-acting beta-2 agonists, anticholinergics (muscarinic receptor antagonists), and high doses of theophylline. Notably, the spotlight rests on long-acting inhaled drugs, such as Long-Acting Beta 2-Agonists (LABA) like formoterol, salmeterol, indacaterol, and Long-Acting Muscarinic Antagonists (LAMA) like tiotropium bromide.

Long-acting inhalants are generally the preferred choice among bronchodilators. These drugs hold sway due to their sustained impact, offering benefits over an extended period. Formulations like LABA and LAMA have become favored choices in managing COPD, reflecting their efficacy in providing relief and improving lung function.

9.1.4 Wide spectrum of choices

The market offers a diverse range of bronchodilators tailored to the needs of COPD patients. Each holds unique features, and the selection process involves matching patient characteristics with the optimal bronchodilator.

This section uncovers the pivotal role of bronchodilators in of COPD management. From their impact on lung function to their potential to enhance overall well-being, bronchodilators stand as essential allies in the fight against the challenges posed by this intricate respiratory condition.

9.2 Anticholinergics: mastering airway control in COPD treatment

9.2.1 Origins and mechanism

The mechanisms through which anticholinergics are beneficial in COPD therapy are not yet fully elucidated. Initially, atropine, a natural compound, entered the scene for asthma treatment. Yet, due to its drying side effects, more soluble compounds like ipratropium bromide emerged. Anticholinergics, with their unique approach, rise as among the most efficacious bronchodilators for COPD. Notably, it is the vagal cholinergic tone that appears to be the only reversible element in the airflow obstruction seen in COPD [22].

9.2.2 Controlling airway tone

A subtle broncho-motor tone is present even at rest, thanks to tonic cholinergic nerve impulses. These nerve signals release acetylcholine near airway smooth muscles. Cholinergic reflex bronchoconstriction can be triggered by irritants, cold air, and stress. Anticholinergics come to the rescue by acting on small airways, minimizing air trapping, and consequently alleviating the burden of dyspnea and its symptoms.

9.2.3 Variety and efficacy

Notable anticholinergic medications like ipratropium bromide and tiotropium bromide are inhaled three to four times a day. On the horizon shines tiotropium bromide, administered once daily. The potency of tiotropium in enhancing lung function and quality of life spans all stages of COPD. Its efficacy remains impressive even when used alongside other therapies, as evidenced by the extensive UPLIFT study [23].

Remarkably, tiotropium brings a cascade of benefits, from reducing severe exacerbations and hospital admissions to curbing mortality due to COPD and cardiovascular disease [24].

9.2.4 Combination and tolerance

Anticholinergics and beta-2 agonists have synergistic benefits. Combining these treatments can offer additive bronchodilation effects. A blend of ipratropium and salbutamol in short-acting inhalers is popular. On the horizon, once-daily combination inhalers merging tiotropium with formoterol promise a new dimension in COPD care.

9.2.5 Safety and side effects

Safety considerations guide us in exploring anticholinergic tolerability. Inhalation of these drugs is well received, with systemic side effects remaining rare due to limited absorption. A unique highlight emerges as we dissect the effects of ipratropium bromide. Even in higher doses, it exerts minimal influence on airway secretions. However, nebulized ipratropium bromide, may trigger glaucoma in the elderly by affecting the eye directly. Notably, the implementation of a mouthpiece circumvents this risk. Dry mouth, a relatively common side effect, is observed in about 10% of that taking tiotropium bromide, seldom necessitating treatment discontinuation.

9.3 Beta-2 agonists

Beta-2 agonists serve as integral components of COPD management. Short-acting variants provide on-demand symptom relief, with the potential for regular use up to four times daily. However, LABA take precedence in COPD therapy, ensuring superior symptom control and maintenance. These agents exert multiple beneficial effects on the airways, inducing relaxation in both large and small airways by interacting with airway smooth muscle. Functioning as antagonists, they proficiently counteract bronchoconstriction, independent of its source. Experimental evidence reveals their prowess in reducing plasma exudation, reducing cholinergic reflexes, and even increasing mucociliary clearance when diminished. While not affecting chronic inflammation, they show promise in mitigating bacterial adherence to airway epithelial cells, potentially reducing infective exacerbations. Moreover, beta-2 agonists may amplify the ventilatory drive to hypercapnia, although the hypoxia response remains largely unchanged. Generally well-tolerated, side effects like muscle tremors, tachycardia, hypokalaemia, and restlessness occur with modest frequency. Importantly, excessive use does not appear detrimental, even in individuals with hypoxia and cardiovascular issues. Occasional hypoxemia may stem from a pulmonary vasodilatation-induced V/Q mismatch [25].

9.3.1 Short-acting beta 2-agonists

Short-acting inhaled beta 2-agonists (SABA) provide more immediate symptom relief. These agents include salbutamol and terbutaline. These agents are meticulously crafted to swiftly alleviate the burden of breathlessness and discomfort experienced by patients. Salbutamol and terbutaline take centre stage as potent solutions, designed to ease distress as required. An important consideration is that, regular usage may lead to the development of tolerance to their protective effects. Therefore, they are ideally used judiciously to avoid diminishing efficacy over time.

9.3.2 Long-acting inhaled beta 2-agonists

This section considers the use of the LABAs, salmeterol and formoterol in COPD management. With an efficacy spanning over 12 hours, these agents stand as defenders, providing sustained bronchodilation and guarding against bronchoconstriction. These agents are potent bronchodilators that also offer a range of benefits, from improved symptom relief, elevated quality of life, and enhanced exercise performance, to alleviation of airway obstruction in smaller passages. Illuminated by extensive long-term studies, their safety and ability to reduce exacerbations and even mortality underscore their vital role. The combined use of these agents with anticholinergics potentially leads to amplified advantages. Moreover, their interaction with bacterial adhesion sparks interest, raising the possibility of lowered infective exacerbations.

9.3.3 Oral beta-2 agonists

Oral beta-2 agonists provide an alternative avenue of relief for elderly individuals encountering challenges with inhaler use. While inhaled beta-2 agonists maintain preference, our focus shifts to the potential of slow-release oral preparations, including bambuterol and slow-release salbutamol. The advantages of these lie in their potential to target peripheral airways more effectively. However, this benefit comes with the trade-off of increased side effects compared to inhaled options. Central to this discussion is bambuterol, a prodrug that transforms into terbutaline, providing an effective once-daily regimen tailored for COPD management.

9.3.4 Theophylline

Operating in higher doses, theophylline’s administration, particularly through oral means, showcases its potential to address the challenges of small airways, while also influencing mucociliary clearance and respiratory muscles. Recent insights reveal its anti-inflammatory capabilities, particularly in reducing neutrophilic inflammation in COPD patients. Theophylline’s mechanisms encompass non-selective phosphodiesterase inhibition, elevated cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) concentrations, and adenosine receptor antagonism. Theophylline’s potential in reversing corticosteroid resistance adds to its complexity. For practical implementation, theophylline finds a place as an additional bronchodilator, often considered for patients unresponsive to regular inhaled anticholinergics and LABAs. Recommendations suggest utilizing slow-release formulations twice daily to achieve desired plasma concentrations. As its anti-inflammatory and corticosteroid resistance-reversing properties come to light, theophylline’s horizon in COPD management expands, potentially prompting the consideration of low-dose usage in conjunction with inhaled corticosteroids [26, 27].

9.3.5 Doxophylline

Doxophylline emerges as a methylxanthine akin to theophylline, boasting comparable bronchodilator attributes. Unlike theophylline, doxophylline stands apart as it refrains from adenosine receptor antagonism, mitigating concerns about cardiac arrhythmias or seizures. Moreover, the advantage of diminished drug interactions further enhances its profile.

9.4 Corticosteroids

The utilization of corticosteroids for COPD management remains a subject of ongoing debate. While the application of oral corticosteroids for maintenance treatment is discouraged due to limited benefits and substantial associated risks in the COPD population, inhaled corticosteroids are frequently prescribed at high doses under the presumption that COPD shares characteristics with refractory asthma. However, evidence supporting their efficacy in pure COPD cases is limited. Roughly 10% of COPD patients exhibit a positive response to oral corticosteroids, indicative of potential coexisting asthma; this subgroup may be better suited for regular inhaled corticosteroid treatment, recognizable through elevated eosinophil counts in sputum.

COPD patients generally show a subdued response to corticosteroids in contrast to asthma, with minimal improvements in lung function. While high-dose inhaled corticosteroids consistently exhibit a 20–25% reduction in exacerbations among severe cases, this stands as their primary clinical application.

The potential reduction in exacerbation frequency might be counterbalanced by systemic adverse effects like osteoporosis, especially among the elderly who may have inadequate nutrition and limited mobility. Indications of increased cataract occurrence and reported pneumonia among COPD patients are associated with high-dose inhaled corticosteroids, further adding complexity to their role. Consequently, the use of inhaled corticosteroids in non-reversible COPD remains uncertain, advocating for lower doses with reduced side effect risks; budesonide might offer a safer option compared to fluticasone propionate [28].

9.5 Combination inhalers

The integration of corticosteroids and LABAs in combination inhalers has garnered attention within COPD treatment, backed by various studies showcasing their advantages. However, the lion’s share of benefits emanates from LABA component, with the combination’s superiority over standalone LABA for reducing exacerbations potentially offset by escalated side effects due to corticosteroids [29]. Notably, combination inhalers not only ameliorate symptoms and curb exacerbations but also exhibit a discernible reduction in all-cause mortality, albeit narrowly missing statistical significance. The exacerbation reduction observed with twice-daily fluticasone/salmeterol approximates that of tiotropium, unveiling a comparable efficacy. These combination inhalers may prove invaluable for individuals with FEV1 less than 50% predicted, marked by frequent exacerbations (less than two per year), who are already on tiotropium and require supplemental treatment [30, 31].

9.6 Supplementary oxygen

Swift administration of controlled oxygen (24%) is pivotal in managing acute exacerbations, serving as a standard practice for hospitalized patients. Furthermore, Long-Term Oxygen Therapy (LTOT), also known as domiciliary oxygen, holds promise for specific COPD cases. Rigorous investigations through expansive multicentre trials have unveiled the life-extending potential of prolonged oxygen supplementation (less than 15 hours daily), manifesting a remarkable survival extension of approximately 30% in COPD patients. A cardinal objective of oxygen therapy is the elevation of PaO2 levels above the 60 mm Hg threshold or the attainment of an oxygen saturation exceeding 90%. However, caution prevails in pushing PaO₂ beyond the 60 mm Hg mark, as additional benefits become marginal while the risk of CO₂ retention escalates. Vigilant evaluation is indispensable before prescribing supplementary oxygen, as its use in patients with CO₂ retention warrants meticulous assessment to circumvent the peril of triggering respiratory failure [32].

9.6.1 Patient selection for Long-Term Oxygen Therapy (LTOT)

The criteria for LTOT suitability can be categorized as absolute and relative indications. The former encompasses scenarios such as

• Stable COPD over a three-week period under optimal therapy, coupled with hypoxemia and edema.

• FEV1 below 1.5 L and FVC below 2.0 L.

• PaO₂ below 55 mm Hg (<7.3 kPa)

• PaCO₂ exceeding 45 mm Hg (>6 kPa).

• Stability over a three-week period under optimal therapy is requisite.

• A relative indication is the need for palliative therapy.

The efficacy of portable oxygen should be gauged through the treadmill or six-minute walk test. Furthermore, individuals grappling with profound exercise limitations independent of oxygen desaturation may benefit from portable oxygen. This consideration extends to circumstances like commercial air travel, where the provision of portable oxygen is facilitated by the airline industry.

9.6.2 Provision of oxygen: diverse approaches and delivery methods

Diverse methods exist for furnishing supplementary oxygen, each tailored to specific circumstances:

Compressed gas cylinders: 100% oxygen stored in these cylinders necessitates frequent replenishment due to their bulkiness and weight. They are equipped with flow meters that offer either medium (2 l/min) or high (4 l/min) settings.

Oxygen concentrators: representing an economical and convenient choice for home-based LTOT, these devices stand as a practical means of oxygen delivery.

Liquid oxygen: carrying portability as an advantage, liquid oxygen is more expensive. Compact units weighing approximately 3 kg can provide oxygen for up to 14 hours at a flow rate of 2 l/min.

The avenues through which oxygen is dispensed include:

Face masks: while efficacious, close-fitting masks prove cumbersome and less suitable for prolonged usage due to discomfort.

Nasal cannula: commonly employed for oxygen delivery, these tubes are generally trouble-free. A flow rate of 1.5 l/min to 2.5 l/min is typically adequate to attain a PaO₂ exceeding 60 mm Hg (8 kPa). Supplement oxygen can cause nasal dryness and nasal irritation. Cold bubble humidification of low flow oxygen therapy via a nasal cannula did not produce any effect on the nasal mucosa and did not attenuate the oxidative stress caused by oxygen. However, it was able to improve nasal symptoms arising from the use of oxygen therapy [33].

Transtracheal catheter: Transtracheal Oxygen Therapy (TTOT) finds utility among select individuals unable to accommodate masks or nasal cannulas.

Pulsed delivery systems: incorporating technology like thermistors or pressure valves, these systems administer oxygen exclusively at the onset of inhalation. While costlier, they markedly curtail oxygen consumption by over one-third.

9.7 Antibiotics

Given that infection often triggers deterioration in COPD patients, effectively addressing infections through antibiotics is a crucial therapeutic aspect. Frequently, the organisms causing pulmonary infections are similar to those inhabiting the upper respiratory tract. Distinguishing if a pathogen in the sputum is the culprit behind exacerbation can be intricate, particularly as sputum color shifts to yellow or green during infection flare-ups, signifying empirical antibiotic initiation. Sputum purulence can result from neutrophil degranulation, which might not invariably signify bacterial infection. In fact, numerous COPD exacerbations likely stem from upper respiratory tract viruses, like Rhinovirus, Coronavirus, and Parainfluenza virus, making it challenging to differentiate between viral and bacterial origins [34]. The incidence of UTI increased over time in men and women with and without COPD. It was higher among men COPD patients than among non-COPD men [35].

While antibiotics are sometimes inappropriately employed, a meta-analysis of placebo-controlled trials for COPD revealed a minor yet significant Peak Expiratory Flow (PEF) discrepancy between antibiotic and placebo-treated patients. Notable bacterial culprits of COPD exacerbations encompass Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and occasionally Mycoplasma pneumoniae. Antibiotic selection hinges on likely pathogens, their community sensitivities, patient tolerance, and treatment response [36].

Preferred community treatments frequently involve amoxicillin or co-trimoxazole (Septrin), although the latter’s use is discouraged due to resistance development and sulfonamide-related side effects. As many H. influenzae strains now produce beta-lactamase, curbing ampicillin/amoxicillin efficacy, initial therapy options often entail:

• Amoxicillin/clavulanic acid (Augmentin).

• Erythromycin or other macrolides (clarithromycin, azithromycin).

• A cephalosporin, e.g., cefaclor.

• A tetracycline, e.g., doxycycline.

Each drug presents pros and cons, and the optimal choice may depend on individual patient response, along with economic factors. Generally, amoxicillin, clavulanic acid, or doxycycline suffice for most ambulatory patients. Antibiotics should be administered at full therapeutic doses over approximately 10–14 days, with clarithromycin and azithromycin requiring shorter courses (3 days). Treatment cessation is warranted upon favorable response; inadequate responses might necessitate a switch to newer broad-spectrum agents like clarithromycin. Sustained antibiotic use is discouraged as it does not modify COPD progression and may foster antibiotic resistance [37].

9.8 Other drug therapies

Exploring mucolytic approaches in COPD management.

Mucus hypersecretion, a prevalent hallmark of chronic bronchitis, has prompted the exploration of various mucolytic therapies aimed at facilitating mucus expectoration, with the ultimate goal of potentially improving lung function. These approaches encompass a range of strategies, each with its own merits and limitations.

Stopping smoking, the most effective intervention stands as the cornerstone in mitigating mucus hypersecretion. Alongside this, anticholinergics have been investigated for their potential to reduce mucus hypersecretion, while beta-2 agonists and theophylline show promise in enhancing mucus clearance.

While certain drugs like bromhexol and ambroxol can decrease mucus viscosity in laboratory settings, their efficacy in improving lung function in COPD patients through controlled trials remains limited, leading to their exclusion as routine therapies. Similarly, expectorants such as guaifenesin and potassium iodide do not present proven beneficial effects.

9.8.1 Antioxidants

With the recognition of oxidant damage’s potential role in COPD pathophysiology, antioxidant therapy has emerged as a logical avenue. N-acetylcysteine and carbocisteine initially designed as mucolytics, exhibit well-documented antioxidant properties. While initial meta-analyses hinted at NAC’s efficacy in reducing COPD exacerbations by approximately 25%, large prospective trials have been less conclusive. A study in treatment-naïve patients from China revealed that carbocisteine demonstrated a reduction of approximately 25% in exacerbations over a year, suggesting a potential benefit for mucolytic/antioxidants in patients not on inhaled corticosteroids [38, 39].

9.8.2 Vaccines

Vaccination strategies offer a crucial defense against infections that trigger severe COPD exacerbations. Influenza vaccination holds significant importance due to its potential to reduce acute exacerbations and hospital admissions. Notably, evidence indicates reduced all-cause mortality in COPD patients following influenza vaccination, making it a cost-effective measure. Pneumococcal vaccination serves as a cost-effective method against pneumococcal lung infections, though large-scale trials for exacerbation reduction are inconclusive [40, 41].

9.8.3 Neuraminidase inhibitors

The application of neuraminidase inhibitors like inhaled zanamivir and oral oseltamivir in speeding up influenza recovery warrants attention. However, the specific impact of these inhibitors in COPD remains uncertain, as dedicated trials in this population are lacking, leaving the cost-effectiveness of this approach yet to be determined [42].

9.8.4 Antitussives

Cough, a frequently bothersome symptom in COPD, holds a potential protective role in facilitating secretion clearance. Consequently, the routine use of antitussives is not advised in the management of COPD (Table 1) [43].

Medications	Examples	Benefits	Side effects
Short Acting Beta-2 Agonist (SABA)	Albuterol Levalbuterol Pirbuterol Terbutaline	Bronchodilation rapid relief of symptoms, reduces anxiety, first-line rescue medications, alternative to oral steroids, portable and convenient	Tremors Nervousness Headache Tachycardia Palpitations Muscle cramps Dizziness Nausea Insomnia Irritation of the throat or mouth
Long Acting Beta-2 Agonist (LABA)	Salmeterol Formoterol Indacaterol Olodaterol Vilanterol	Extended bronchodilation, reduced symptoms, improved lung function, enhanced exercise tolerance, decreased exacerbations, better quality of life	Tremors Tachycardia Palpitations Headache Muscle cramps Dizziness Nausea
Oral beta 2 agonist	Carbuterol Pirbuterol Procaterol Bitolterol Clenbuterol	Quick symptom relief, bronchodilation, improved airflow, exercise tolerance, reduction in anxiety, first-line rescue medication, combination therapy, easy to administer	Tremors Headache Dizziness Nausea Changes blood pressure Restlessness Sweating Palpitations Digestive issues Dry mouth
Long Acting Muscarinic Agents (LAMA)	Tiotropium Aclidinium Umeclidinium Glycopyrrolate Revefenacin	Prolonged bronchodilation, improved airflow, reduced breathlessness, enhanced exercise tolerance, maintenance therapy, reduced exacerbations, convenient dosing, complementary to other COPD medications, better quality of life	Dry mouth Constipation Urinary retention Blurred vision Dry eyes Tachycardia Headache Sore throat Allergic reactions Bronchospasm (rare)
Theophylline	Aminophylline Theo-Dur	Bronchodilation, improved lung function, long-acting add-on therapy, reduced breathlessness, emergency use, potential anti-inflammatory effects, cost-effective, alternative for some patients	Headache Insomnia Irritability Nausea Vomiting Diarrhea Restlessness Tachycardia Tremors Dizziness Palpitations Changes in blood pressure Increased urination seizure High calcium levels Difficulty urinating (elderly males with prostatism)
Doxyphylline	Brand Names; Doxolin Duracron	Bronchodilation, symptom relief, reduced breathlessness, alternative to theophylline with potentially fewer side effects, option for patients who may not tolerate other bronchodilators	Headache Nausea Vomiting Insomnia Epigastric pain Irritability Tachycardia Tachypnea
Cortico-steroids	Inhaled cortico-steroids Beclomethasone Budesonide Fluticasone Ciclesonide Oral cortico-steroids Prednisone Methyl-prednisolone Prednisolone Systemic cortico-steroids Hydrocortisone Methy-lprednisolone	Reduced airway inflammation, symptom control, exacerbation prevention, acute exacerbation treatment, enhanced response to bronchodilators, quality of life improvement, reduced hospitalizations	Oral thrush Hoarseness sore throat Skin changes Cataracts Glaucoma Bone health issues Adrenal suppression Withdrawal symptoms
Combination inhalers	Fluticasone/salmeterol Budesonide/formoterol Fluticasone/vilanterol Fluticasone/vilanterol Glycopyrrolate/formoterol Aclidinium/formoterol Indacaterol/glycopyrrolate Tiotropium/olodaterol Umeclidinium/vilanterol	Improved bronchodilation, enhanced lung function, comprehensive symptom control, reduced exacerbations, convenient once-daily dosing, enhanced exercise tolerance	Oral and throat irritation Dry mouth Tachycardia increased risk of pneumonia Hoarseness and voice changes Headache Muscle cramps Osteoporosis Cataracts Thrush
Oxygen therapy	Target SpO2 85–88% and use appropriate oxygen delivery device according to it	Improved oxygenation, reduced shortness of breath, increased exercise tolerance, improved sleep quality, enhanced quality of life	Dry or irritated nasal passages Nasal congestion Oxygen toxicity Oxygen induced hypoventilation Skin irritation Claustrophobia
Antibiotics	Azithromycin Clarithromycin Erythromycin Amoxicillin Doxycycline Levofloxacin Moxifloxacin Ciprofloxacin	Infection control; Reduction in exacerbation severity; Faster recovery	Nausea Diarrhea Abdominal pain Allergic reactions Rashes Headache Dizziness Change in taste
Mucolytics	N-acetylcysteine Dornase alfa	Thinning and loosening of mucus; Easier clearance of mucus from the airways	Nausea Vomiting Stomach discomfort
Antioxidants	N-acetylcysteine (NAC) Alpha-lipoic acid (ALA)	Potential reduction in oxidative stress and inflammation	Generally considered safe when taken within recommended doses
Vaccines	Influenza (Flu) vaccine Pneumococcal vaccine	Prevention of specific respiratory infections (e.g., influenza, pneumonia); Reduced risk of exacerbations in COPD patients	Mild, temporary discomfort at the injection site Rare allergic reactions
Neuraminidase inhibitors	Oseltamivir Zanamivir Peramivir	Reduction in severity and duration of influenza symptoms, potential prevention of influenza infection in COPD patients	Nausea Vomiting Headache Dizziness
Antiussives	Dextromethorphan Codeine	Reduction in cough reflex; Relief from dry, non-productive cough	Drowsiness Dizziness Nausea

Table 1.

Summary of COPD drug treatment, benefit and side effect.

9.9 Non-pharmacological approaches in COPD management

9.9.1 Exercise

Physical exercise training, regardless of the specific type, is valuable for improving cardiorespiratory function in COPD. Both aerobic and upper limb exercises yield similar efficacy. Incorporating respiratory muscle training through resistive inspiratory loading can alleviate breathlessness, although comprehensive evidence from controlled studies remains inconclusive. Controlled breathing techniques like pursed-lip and diaphragmatic breathing show promise in reducing dyspnea, particularly in patients prone to hyperventilation [44].

9.9.2 Nutritional considerations

Nutrition is paramount in COPD management due to prevalent malnutrition and underweight status, though marked cachexia is now less frequent. Obesity may affect certain patients due to reduced physical activity. Addressing weight loss is crucial, especially for those with sleep disturbances, metabolic syndrome, or type II diabetes. Antioxidant vitamin supplements can also be beneficial. Nevertheless, high-fat nutritional supplements marketed for COPD have yet to demonstrate clear advantages [45].

9.9.3 Pulmonary rehabilitation

Rehabilitation endeavors to avert deconditioning and enhance the patient’s capacity to manage their condition. Successful rehabilitation programs have proven to improve performance and quality of life, though not necessarily lung function. Patients with moderate-to-severe COPD are suitable candidates for pulmonary rehabilitation, encompassing educational guidance and physiotherapy. Notably, pulmonary rehabilitation synergizes with bronchodilator therapy [46].

9.9.4 Artificial ventilation

Remarkable progress has occurred in artificial ventilation devices. Nasal intermittent positive pressure ventilation has revolutionized COPD care, aiding both acute exacerbations management in hospitals and controlling hypercapnic respiratory failure at home. This technique ameliorates hypercapnia and respiratory acidosis, and grants rest to respiratory muscles. Positive outcomes have been noted, manifesting as reduced mortality and hospitalization periods during acute exacerbations [47].

9.9.5 Surgical options

For severe emphysema cases, various surgical interventions have exhibited success. Heart-lung transplantation, once predominant, has been largely replaced by single-lung transplantation in carefully chosen patients. Lung volume reduction surgery (LVRS) involving the excision of extensively affected emphysematous lung proves effective for selected individuals with primarily upper lobe emphysema and air trapping evidence. Patients without a barrel-shaped chest are significantly less likely to have airflow limitation.

LVRS yields sustained lung function enhancement, symptom reduction, and fewer exacerbations. However, very poor diffusing capacity increases mortality risk, underscoring the importance of patient selection. Recently, bronchoscopic lung volume reduction surgery methods have emerged to minimize the surgical complications of LVRS. Several devices, including valves, coils, and non-blocking techniques like bronchoscopic thermal vapor ablation and polymeric lung volume reduction, are currently under development to collapse and remodel hyperinflated lung regions [48].

9.10 Managing acute exacerbations

9.10.1 Preventive measures

A pivotal objective in COPD treatment is preventing exacerbations. Numerous interventions demonstrated through controlled trials to diminish exacerbation rates and hospitalization encompass long-acting bronchodilators (beta-2 agonists and anticholinergics), low-dose theophylline, high-dose inhaled corticosteroids, and smoking cessation.

9.10.2 Exacerbation implications

COPD exacerbations stand as a prime reason for hospital admissions. Beyond addressing underlying bacterial infection with antibiotics as previously discussed, exacerbations warrant symptomatic management, involving escalated doses of SABA and anticholinergic bronchodilators administered through nebulization. The role of antibiotics remains ambiguous due to limited clinical benefit in controlled trials, largely owing to the multifaceted origins of exacerbations, with over half stemming from viral or non-infectious causes.

9.10.3 Symptomatic management

To stabilize patients, oxygen administration (using a 24% or 28% Venturi mask) should attain a PaO₂ of at least 60 mm Hg without causing pH to drop below 7.26 (indicating acute alteration). Oxygen therapy’s effectiveness should be assessed within an hour through blood gas analysis. Pulse oximetry may be employed for oxygen saturation monitoring, provided PaCO₂ and pH are within normal limits. Typically, a course of oral corticosteroids is recommended, marginally shortening in-patient stays by about 1 day. Extremely high doses of corticosteroids, like intravenous methylprednisolone, are usually unnecessary due to elevated side effect risks. Diuretics are suitable for peripheral edema. While chest physiotherapy may have value, evidence from controlled studies verifying its recovery-enhancing effect is scarce. Instances of rising PaCO₂ prompting respiratory failure might necessitate NIPPV or intubation.

9.11 Managing chronic disease

9.11.1 Accurate diagnosis and differentiation

Achieving an accurate diagnosis and distinguishing COPD from asthma is essential, typically discernible through patient history. Spirometry plays a pivotal role in objectively diagnosing airway obstruction and staging the disease, facilitating the selection of optimal therapeutic approaches. The GOLD guidelines delineate a stepwise escalation strategy for COPD treatment based on disease severity [49].

9.11.2 Foundational interventions

Throughout all stages, smoking cessation is paramount, especially in the early disease phases. Patients should routinely receive seasonal influenza immunization to mitigate complications. For GOLD stage 1, characterized by minimal functional impairment, treatment mainly involves as-needed inhalation of short-acting bronchodilators like salbutamol, ipratropium, or their combination.

In GOLD stage 2, a long-acting bronchodilator, such as tiotropium once daily or salmeterol/formoterol twice daily, is preferred. The once-daily regimen is often preferred by patients. If long-acting bronchodilators are financially unfeasible, regular administration of short-acting bronchodilators (e.g., salbutamol or ipratropium bromide), four times daily, or oral bronchodilators like slow-release theophylline or once-daily bambuterol, might be necessary. In some cases, a combination of long-acting anticholinergic and LABA is prescribed, preferably in a combination inhaler.

9.11.3 Advancing treatment

For GOLD stage 3 patients, the addition of inhaled corticosteroids (ICS) is considered, often through combination inhalers with a steroid and LABA. Additionally, oral theophylline may be introduced at this juncture due to its potential anti-inflammatory effects. Availability permitting, pulmonary rehabilitation could be beneficial. In GOLD stage 4, supplementary oxygen and, in carefully selected cases, lung surgery should be contemplated.

10. Conclusion

COPD is the most common respiratory diseases associated with high mortality and morbidity. There are many new treatment options present from oral pharmacological to surgical interventions that help the patient to improve the conditions. Pulmonary rehabilitation techniques are newer. A multidisciplinary approach helps the patient in an effective and efficient way. Continued advances in treatment should be made to improve the long term clinical outcomes and decrease the course of diseases.

Acknowledgments

I Abu Talha Hanfi wish to register my profound gratitude to Almighty for guidance and grace throughout my life. I would also like to extend regards to my amazing parents who are the source of success in my life. I would like to thank my wife.

The world is a better place to live. Thanks to people who want to develop and lead others. Thank you to everyone who strives to grow and help others grow.

Abbreviations

GOLD	Global initiative for Chronic Obstructive Lung Disease
COPD	chronic obstructive pulmonary diseases
AATD	alpha-1 antitrypsin deficiency
ETS	environmental tobacco smoke
FEV1	forced expiratory volume
MMRC	Modified Medical Research Council
FVC	forced vital capacity
CAT	COPD Assessment Scale
LABA	Long-Acting Beta 2-Agonists
LAMA	Long-Acting Muscarinic Antagonists
cAMP	cyclic adenosine monophosphate (cAMP)
cGMP	cyclic guanosine monophosphate
LTOT	Long-Term Oxygen Therapy
TTOT	Transtracheal Oxygen Therapy
PEF	Peak Expiratory Flow
ICS	inhaled corticosteroids