To measure forced vital capacity (FVC) using spirometry, the patient must start by taking a deep breath. Afterward, they should exhale forcefully and for as long as they can manage. The amount of air exhaled during this maneuver is the FVC. The Forced Expiratory Volume in one second (FEV1) is the volume of air that can be forcefully exhaled in the first second of a Forced Vital Capacity (FVC) maneuver. This measurement is often lower in patients with obstructive respiratory diseases like asthma or emphysema. The FEV1/FVC ratio assesses whether the respiratory pattern is obstructive, restrictive, or normal [7].

The term PRISm has been proposed to identify patients who do not have Forced Expiratory Volume in the first second (FEV1)/ Forced Vital Capacity (FVC) < 0.7 post bronchodilation but have abnormal spirometry (FEV1 < 80% of reference post-bronchodilator) [8]. Almost a quarter of these patients develop fixed airflow obstruction in the succeeding 4-5 years, which could represent an opportunity to reduce disease [9, 10].

The presence of emphysema in CT chest aids in diagnosis when spirometry is not diagnostic, and it can predict a rapid decline in FEV1 and indicate a higher risk of malignancy [13]. Detection of bronchiectasis in COPD, which is reported to be around 30% on CT chest, also predicts recurrent exacerbations and higher mortality [6, 14]. Lung cancer screening guidelines with low-dose chest CT scans increase emphysema detection and characterization. CT chest also helps in lung volume reduction surgery (LVRS) or endobronchial valve planning.

However, there is no role for routine CT chest scans in all patients with COPD.

ABCD tool, included in the GOLD guideline prior to 2023, combined FEV1 with measures of disease severity that included episodes of COPD exacerbations, hospitalization, and patient functional status [15]. It has laid more emphasis on the “treatable” traits of COPD, such as the burden of symptoms and exacerbation history (Fig. 1).

GOLD 2023 guideline has now phased out categories C and D in the assessment tool and replaced them with a single category E. Patients with no exacerbation or only one exacerbation not leading to hospital admission fall into category A or B. Patients are categorized as A if their mMRC scale is 0-1 or their COPD assessment tool (CAT) score is less than 10. Patients fall into category B if their mMRC scale is 2 or more or their CAT score is 10 or more [16]. This has not changed as compared to previous guidelines. Patients in category A have mild symptoms and typically should be managed with bronchodilators. Patients in category B are more symptomatic and treatment recommendations include dual long-acting bronchodilator therapy (long-acting beta-2 agonist, LABA/ Long-acting muscarinic antagonist, LAMA). Category E includes all patients with a history of two or more exacerbations or one or more exacerbations leading to hospitalization. (Fig. 1) [5]. The more severe Category E patients should be started on dual bronchodilator therapy (LABA/LAMA). If the blood eosinophil count is ≥ 300 cells/microliter, then the recommendation is to consider a triple therapy combination of LABA/LAMA and Inhaled corticosteroid (ICS) (Fig. 1).

Fig. (1). Shows a simple recreation of ABE assessment tool and pharmacological options based on 2023 GOLD guidelines.

Two landmark studies influenced the management of GOLD group E patients.In the Informing the Pathway of COPD treatment (IMPACT) trial, triple inhalers (LABA/LAMA/ICS) decreased moderate to severe COPD exacerbations by 25 and 15% annually compared to LABA/LAMA and LABA/ICS, respectively [17]. The study also showed 54 ml (on average) improvement in FEV1 at the 12-month endpoint compared to LABA/LAMA and 97 ml compared to LABA/ICS. 42% of patients on triple inhalers had a four or more-point decrease in St. George's Respiratory Questionnaire (SGRQ) compared to 34% each in patients on LABA/LAMA and LABA/ICS inhalers [17].

Thus, there was an overall improvement in quality of life with the triple inhaler. The Efficacy and Safety of Triple Therapy in Obstructive Lung

The disease (ETHOS) trial also tested triple inhalers with LABA/LAMA and LABA/ICS. The annual moderate to severe COPD exacerbation rate was 1.07 in the low-dose triple inhaler group compared to 1.42 in LABA/LAMA and 1.24 in LABA/ICS group [18].

A notable change in the new guidelines is the elimination of groups C and D, including the more severe patients. There was a likelihood of misclassification of patients to group C based on improper perception and reporting of symptoms by the patients [19]. Thus, the abolishment of categories C and D and the creation of E have lumped patients with greater symptom burden and exacerbation risk under the same umbrella. This facilitated streamlining the correct use of long-acting bronchodilators and inhaled corticosteroids in COPD. ICS/LABA combination now does not play any role in patients with COPD without asthma. Real-life experiences using these recommendations will inform us about the impact of these significant changes, but they also raise important questions.

(a) What would be the recommendation by GOLD for resource-limited countries and communities where provision for even essential medicines is still a challenge?

(b) What challenges would be with patents for manufacturing triple inhaler therapies for developing nations [20]?

(c) How widely will the paradigm shift from using ICS/LABA to only using LAMA/LABA or triple therapy be accepted?

With the recognition that an exacerbation represents a major change in the disease trajectory, the 2023 guideline has come up with a new definition for the exacerbation of COPD. It is now defined as “an event characterized by dyspnea and/or cough and sputum that worsen over < 14 days. It may be associated with tachypnea or tachycardia” [21]. The notion of systemic or local inflammation instigated by an airway infection, pollutants, or other triggers has been implicated in COPD exacerbation. The emphasis is on the etiology and triggers of COPD exacerbation similar to the section in the definition of COPD in a stable patient. Addressing confounding factors such as pneumonia, pulmonary embolism, congestive heart failure, acute coronary syndrome, pleural effusion, and pneumothorax set treatment priorities.

Intervention for COPD exacerbation based on 2022 recommendations of mild, moderate, and severe classification has also seen a proposed change in the current guidelines. Scoring of different variables threshold that includes visual analog dyspnea scale, respiratory rate, heart rate, oxygen saturation, C-reactive protein, partial pressure of Oxygen, and partial pressure of carbon dioxide has been used to stratify the severity (Table 2) [21]. There were no major changes in the treatment strategy for COPD exacerbations. This guideline has outlined follow-up recommendations for the first 1-4 weeks and 12-16 weeks of hospital discharge in COPD patients with spirometry (Tables 3 and 4). Overall, the follow-up instructions should help reduce re-hospitalization and provide a better transition of care.

It is well known that hyperinflation is a significant feature of COPD. It is established that lung volume reduction surgery (LVRS) improves chest wall and diaphragm mechanics by removing hyperinflated lungs in selected patients with COPD. However, LVRS can be associated with significant morbidity and mortality [22]. Endoscopic lung volume reduction (ELVR), encompassing means like endobronchial valves (EBV), sealants, and vapor ablation (VA), has been suggested by this report as a viable alternative to LVRS mainly due to less morbidity and mortality [22]. EBV is a device that prevents air entry during inspiration but allows the one-way escape of air and secretions during expiration, thereby promoting atelectasis of the hyperinflated part of the lung. Lung sealants such as a mixture of fibrin, polymer, and thrombin can collapse emphysematous areas. Vapor ablation is the direct application of steam vapor by a bronchoscope to induce inflammation and subsequent atelectasis of a lung segment.

A key concept emphasized is the interlobar fissure integrity, which prevents collateral ventilation while describing ELVR choices. If the fissure integrity is > 90% as determined by high-resolution CT chest, EBV, VA, sealants, or LVRS are options for treatment. If collateral ventilation is present, EBV is excluded, while VA, sealants, and LVRS can still be valid options in selected patients [23, 24]. Discussion about nitrogen cryospray (liquid nitrogen application to ablate abnormal epithelium and cause mucosal regeneration) and rheoplasty (pulsed electricity applied by an endobronchial catheter) are recognized as potential treatment options for chronic bronchitis in this current guideline. Similarly, targeted lung denervation to blunt the effect of the parasympathetic nervous system and decrease mucus production has been mentioned for patients with frequent COPD exacerbations [6].

We feel that advanced bronchoscopy in COPD can be an important additional resource for COPD patients not improving on optimal medical treatment and pulmonary rehabilitation. A significant investment in a multidisciplinary team infrastructure with trained interventional pulmonologists is necessary.

Pulmonary rehabilitation consists of exercise training, education for the specific disease process, and learned interventions as a self-management tool [25]. Barriers to utilizing pulmonary rehabilitation include access, availability, and funding. The GOLD guidelines discuss current evidence on Telerehabilitation programs in COPD. In a systematic review published in 2022, ten studies (n=245) were evaluated. There were positive effects of telerehabilitation on functional exercise capacity, anxiety, depression, quality of life, and the overall impact of COPD on a patient's personal life. Interestingly, there was no overall impact on dyspnea [26]. A Cochrane review concluded that telerehabilitation was safe and achieved similar outcomes compared to in-person rehabilitation in patients with chronic respiratory diseases.

However, the limitations include a small number of studies with a high degree of heterogeneity [27]. GOLD 2023 guideline has determined that there is still a need for definite evidence for telerehabilitation.

There is a need for telerehabilitation to be standardized in terms of mode of delivery, exercise prescription, post-COPD exacerbation interventions, and optimal duration for the maximal derivation of benefit. Besides, the technology should be user-friendly and easily accessible.

Due to the outbreak of COVID-19, routine diagnosis and subsequent management of COPD became a challenge. With limited regular in-person office visits, difficulties in performing pulmonary function testing (PFT), and medication shortages, the plight of COPD patients was multifold. GOLD 2023 has discussed the interplay between COPD and COVID-19 [28, 29].

Per GOLD, it is unclear if COPD predisposes patients to a higher risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Even though the results are mixed, the GOLD report includes evidence indicating a higher risk of severe COVID-19 in patients with COPD [30]. After adjusting for the confounding factors, the data included in the GOLD report suggested that there is an overall higher mortality risk in COVID-19 patients with COPD (Odds ratio 1.41, 95% confidence interval 1.37 – 1.65) and intensive care unit admission (Odds ratio 1.25, 95% confidence interval 1.08 – 1.51) [31]. Poor compliance with maintenance therapy in COPD, decreased baseline pulmonary reserve, and difficult access to healthcare resources have been signaled as the predictors of poor outcomes. The guidelines recommend testing even for mild symptoms, considering other co-pathogens during COPD exacerbations, and being alert for relapses in these patients.

GOLD 2023 has suggested limiting PFT to urgent or essential cases for diagnosis of COPD, especially during high COVID-19 prevalence. Reverse-transcriptase polymerase chain reaction (RT-PCR) has been recommended whenever possible before performing PFT during an outbreak [32]. However, these recommendations don’t apply to the current COVID incidence and prevalence. Current evidence suggests continuing corticosteroids and inhaled bronchodilators during COVID-19 infection. The United States Centers for Disease Control and Prevention Advisory Committee of Immunization Practices (ACIP) recommendations for pneumococcal vaccination (pneumococcal conjugate vaccine [PCV] 20 alone or PCV15 followed by pneumococcal polysaccharide 23 vaccine) and yearly influenza vaccine recommendations would not change in COPD patients during COVID- 19 pandemic per GOLD report.

According to the GOLD 2023 report, triple therapy should only be considered a first line of treatment for patients whose blood eosinophil count is ≥300 cells/μL and who have experienced two moderate or one severe exacerbation. Recent research suggests that patients with blood eosinophil counts between 100 and 300 cells/L, especially those who have been hospitalized and are already taking medication, may benefit from adding an ICS to their current treatment plan [33]. More study is required into the use of lower thresholds for triple therapy commencement.

Patients who experience exacerbations are now treated using a follow-up protocol that does not define the severity or frequency of the exacerbations. Clarity regarding how exacerbation severity should affect treatment choices is required, given the correlation between exacerbation severity and the risk of subsequent exacerbations and/or mortality.

Receiving treatment recommendations post-hospitalization would prove to be quite beneficial. Various studies highlight that hospitalizations tend to increase the likelihood of poor outcomes, subsequent hospitalizations and mortality [34, 35]. Research has shown that triple therapy significantly reduces the likelihood of future hospitalizations following moderate and severe exacerbations. The guideline needs to clarify the recommendations that regulate the utilization of triple therapy for patients who have undergone hospitalization due to exacerbation [17, 18].