After the increased interest in infectious diseases and in pneumoconiosis as a respiratory disease, the diseases that caused obstructive ventilatory impairment attracted much interest in the 1950s, after the World War II, because of the development of respiratory tests. In the UK, obstructive ventilatory impairment was primarily diagnosed as “chronic bronchitis” from the symptomatic point of view whereas, in the United States, it was primarily diagnosed as “pulmonary emphysema” from the pathological point of view. The similarities and differences between the two disease entities have been discussed extensively. The landmark meeting conducted in 1959—the CIBA Guest Symposium—and the concept of chronic nonspecific lung disease (CNSLD) helped elucidate the two disease concepts [5]. Fletcher, in the UK, and Burrows, in the United States, defined the concept of obstructive ventilatory impairment and named the group of diseases that caused obstructive ventilatory impairment as chronic obstructive lung disease (COLD) [6]. COLD is characterized by chronic and irreversible airway obstruction. Airflow obstruction is characterized by the narrowing of the airway lumen and reservoir of secretion in lumen due to chronic inflammation of the airways and by the decrease in the lung elastic recoil due to the alveolar destruction. The narrowing of the airway lumen defines chronic bronchitis, whereas the decrease in the lung elastic recoil defines emphysema. Burrow et al. classified COLD into type A (emphysema type), type B (bronchitis type), and type X (intermediate form between types A and B) [3]. On the other hand, Filley et al. classified COLD into type PP (pink puffer) and type BB (blue bloater) [4]. Hogg et al. revealed that the distal airways, which are defined as airways with an inner diameter of 2 mm or less, contributed much more to the total airway resistance in subjects with COLD but contributed less than 20 % in healthy subjects [7]. This observation allowed us to hypothesize that the dysfunction of the distal airways is key for the early diagnosis of COLD. Later, the physiology of the distal airways was investigated. Various parameters in the flow volume curve, such as V25, V50, single-breath nitrogen washout for measuring the closing volume, and the frequency dependence of lung compliance, have been diligently studied to help elucidate the pathophysiology of COLD. However, these attempts failed to reach the initial goal to diagnose COLD earlier because of insufficient sensitivity and specificity due to large variations in the test values and overlap with values from healthy subjects. Therefore, forced expiratory volume in one second (FEV1) or forced expiratory volume in one second % (FEV1/forced vital capacity (FVC)) was used for the diagnosis of COPD. In 1987, the American Thoracic Society changed the name of the disease from COLD to COPD and redefined its concept. Therefore, COPD was redefined as a disease characterized by emphysema, chronic bronchitis, and distal airway dysfunction and was caused by nonreversible airflow obstruction. Following this definition, the GOLD guidelines were published in 2001. Several revisions were made in these guidelines on the basis of the accumulated scientific evidence, and GOLD was last updated in 2016.

Both COPD and bronchial asthma are characterized by obstructive ventilatory impairment, and the underlying condition is airway inflammation. In 1961, Orie et al. hypothesized that chronic bronchitis and emphysema, both of which are now considered COPDs, and bronchial asthma were only phenotypes of the same disease, which was caused by inflammation of the airways, and therefore these conditions should be considered the same disease. The hypothesis was that different environmental factors, including allergens, tobacco, and air pollutants, affected the underlying genetic predisposition for atopic constitution and airway hyperresponsiveness and produced different phenotypes, including bronchial asthma and COPD. This was later referred to as the Dutch hypothesis, and the concept of CNSLD was proposed. Although the most common cause of COPD is smoking, not all of the smokers necessarily develop COPD. The Dutch hypothesis states that the susceptibility for developing COPD in smokers is due to genetic predisposition for atopy. The basis for this hypothesis was that airway hyperresponsiveness, high peripheral blood eosinophilia, and high IgE levels were observed in COPD, and the number of eosinophils in sputum was correlated with an obstructive ventilatory impairment similar to that observed in bronchial asthma. COPD itself sometimes has asthma-like characteristics, and it is known that the development of COPD together with asthma is frequent. A new concept on the development of the asthma COPD overlap syndrome was proposed. In addition to the Dutch hypothesis, the British hypothesis considered that the excessive secretion associated with respiratory tract infection was the leading cause of obstructive ventilatory impairment. The Dutch and British hypotheses were confirmed in studies on bronchial asthma and COPD and helped elucidate the pathogenesis of these diseases.

In the COPD guideline of the Japanese Respiratory Society, COPD is diagnosed using FEV1. However, this guideline also indicates the presence of two phenotypes, distal airway disease and emphysema lesions, which act jointly at various levels and cause airflow limitation. Filley et al. suggest the presence of two different phenotype groups in COPD, i.e., type PP (pink puffer) and type BB (blue bloater) COPD [4]. Pink puffers have a pink complexion and dyspnea. Emphysema-type COPD (in which emphysema lesions are the predominant type) is equivalent to PP-type COPD. PP-type COPD involves severe emphysema, increased residual lung capacity and volume, decreased elastic recoil, decreased diffusing capacity, and a ventilator/perfusion mismatch secondary to emphysema-associated destruction of blood vessels. Arterial blood gas (ABG) is usually near normal owing to compensatory hyperventilation, PaO₂ levels are normal, and PaCO₂ levels are low to normal. Pink puffers have increased tidal volume and retraction of accessory respiratory muscles for compensation. The amount of energy required for respiration causes an imbalance between energy intake and energy consumption. Although subjects with BB-type COPD tend to be normal weight or overweight, those with PP-type COPD tend to be underweight (Fig. 1.2). It has been reported that PP-type COPD is more common than BB-type COPD in Japan. Blue bloaters have cyanosis and right heart failure. Non-emphysema-type COPD (in which distal airway disease is the predominant type) is equivalent to BB-type COPD. Patients with BB-type COPD have cyanosis and chronic bronchitis, normal to low lung capacity, increased residual volume with air trapping, and characteristic ABG, i.e., decreased PaO₂ and increased PaCO₂, although the diffusion capacity is normal. Subjects with BB-type COPD tend to be overweight.

The GOLD program was initiated in 1998 to provide recommendations for the management of COPD on the basis of the best scientific information available. The first report, the Global Strategy for Diagnosis, Management, and Prevention of COPD, was issued in 2001. This report was widely translated into many languages and distributed worldwide and served as a global guideline. The GOLD Scientific Committee launched a joint project between the WHO and the National Heart, Lung, and Blood Institute (NHLBI) in 2002. Its members are recognized leaders in COPD research and clinical practice, with the scientific credentials to review published research on COPD management and prevention, to evaluate the impact of this research on the recommendations proposed in the GOLD guidelines related to management and prevention, and to provide yearly updates on the GOLD website. A complete revision was prepared in 2006, 2011, and 2016 on the basis of published research. With regard to the classification and severity of COPD, a new combined assessment was introduced in 2011 (Fig. 1.3). In the 2011 report, the GOLD Scientific Committee recommends the assessment of COPD on the basis of a combination of factors, including the patient level of symptoms, the future risk of exacerbations, and the severity of the spirometric abnormality; however, the severity of the spirometric abnormality should not be used alone. A previous spirometric classification divided airflow limitation into four grades using the fixed ratio (FEV1/FVC), and airflow limitation was defined as a post-bronchodilator FEV1/FVC < 0.7 (Table 1.1). It has been recognized that the use of the fixed ratio might lead to more frequent diagnoses of COPD in the older population with mild COPD—because the normal aging process affects lung volume and flow—but might lead to underdiagnosis in younger populations. Similarly, the use of the spirometric classification of airflow limitation might lead to the classification of COPD as more severe in older populations and less severe in younger populations. Moreover, the frequent presence of the exacerbation phenotype has been reported [8]. Although acute exacerbations are key events in COPD progression, the determinants of their frequency are poorly understood. Using a large observational cohort, the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study revealed that acute exacerbations are independent of spirometric severity. Although acute exacerbations become more frequent and more severe as the severity of COPD increases, the single best predictor of exacerbations across all GOLD stages is the history of exacerbations, not the severity of COPD (Fig. 1.4). The frequent exacerbation phenotype appeared to be relatively preserved over a period of 3 years (Fig. 1.4). Proper COPD treatment is based on an accurate assessment of the severity of COPD, its impact on the patient’s health status, and the risk of future events such as acute exacerbations, hospital admissions, and death. In the GOLD 2011 assessment, severity alone was not used to achieve proper treatment, but other aspects of COPD were considered separately, including the current level of patient symptoms, severity of the spirometric abnormality, risk of exacerbations, and presence of comorbidities. Several validated questionnaires are available to assess symptoms in patients with COPD. For symptoms, GOLD recommends the use of two well-known questionnaires, the modified British Medical Research Council (mMRC) questionnaire and the COPD Assessment Test (CAT) [9]. Although the mMRC questionnaire only assesses disability due to breathlessness, CAT can assess other measures of health status and predict future mortality risk better than airflow limitation [10]. The CAT provides a broader coverage of the impact of COPD on the patient’s quality of life (QOL). The CAT was developed and validated by Jones et al. [9]. The CAT is an 8-item unidimensional measure of the impairment of the health status in COPD; it has been applied worldwide and its translation has been validated in several languages. Previously used disease-specific questionnaires, such as the St George’s Respiratory Questionnaire (SGRQ) [11], Chronic Respiratory Disease Questionnaire [12], and the COPD Clinical Questionnaire [13], are reliable, validated, and widely used in clinical trials or in clinical practice. However, some of these instruments are lengthy and have highly complex scoring algorithms for routine use in clinical practice. A brief questionnaire that is easy to complete and interpret is necessary for routine use, and the CAT was developed for this purpose. Eight items of the CAT were identified out of 21 candidate items using the psychometric and Rasch analysis, and the correlation (r) with the COPD-specific version of the SGRQ was 0.80 and the internal consistency was excellent [9]. The score ranges from 0 to 40 and can be correlated with the SGRQ scoring. The CAT also performs spirometric assessments to classify airflow limitation severity in patients with COPD. For this purpose, specific spirometric cut points are used for simplicity and the cut-point values are the same as those used previously. To minimize variability, spirometry should be performed after the administration of an adequate dose of a short-acting inhaled bronchodilator. However, there is only a weak correlation between FEV1 and the COPD symptoms that impair the patient’s QOL. For this reason, both symptomatic assessment and spirometric assessment are required.