COPD: Not just a simple disease

In 2016, there are around 251 million cases of chronic obstructive pulmonary disease (COPD) worldwide with 90% of mortality occurring in the low- and middle-income countries, which includes the Philippines. In a Boehringer Ingelheim-sponsored webinar series in partnership with the Philippine College of Chest Physicians on 29 August 2020, 12 September 2020 and 25 September 2020, Dr Ronaldo Majarreis Panganiban, Jr., Director for Finance at the Green City Medical Center and an Active Consultant at the Mother Teresa of Calcutta Medical Center and VL Makabali Memorial Hospital; Dr Sheenly Vi Tenefrancia-Suresca, Pulmonary Section Head at the Medical City in Iloilo and Active Consultant at the West Visayas State University Medical Center, and Dr Lenora Fernandez, Chief of the Division of Pulmonary Medicine at the UP-PGH, Head of the Section of Pulmonology at the Asian Hospital and Past President of the Philippine College of Chest Physician, discussed about the relevance of peak inspiratory flow rate (PIFR) in COPD, COPD guidelines, and the relevance of inhaled corticosteroid in COPD management.


Dr Ronaldo Majarreis Panganiban, Jr.


Dr Sheenly Vi Tenefrancia-Suresca


Dr Lenora Fernandez

Breaking the disengagement spiral of COPD

“COPD is not a simple disease. It is a clinical syndrome,” Dr Fernandez emphasized.

It is a result of an interplay between genes and the environment, with cigarette smoking as the leading risk factor. The noxious stimuli result in inflammation and narrowing of the peripheral airway, which contribute to airflow limitation. These, consequently, lead to hyperinflation and dyspnea and limitation of activities. “As a consequence, the patient adjusts to the situation by limiting their activities and abandoning physical exercise, ultimately leading to inactivity. Disengagement from activities and exercise leads to deconditioning, which actually worsens breathlessness and reduces exercise capacity,” Dr Panganiban explained. “Overall, the quality of life of these [COPD] patients progressively decrease as the disease advances,” he continued. [Global Initiative for Chronic Obstructive Lung Disease. 2020.]

Hence, as Dr Panganiban specified, “Once they [patients with COPD] are diagnosed, once they have symptoms, you need to treat them right away”. However, he pointed out, “patients with COPD live with damaged lungs and many cannot forcefully inhale and yet, the best medication that you can give them are inhalers that may require your patients with COPD to forcefully inhale optimally just to activate their medication”.

Emphasizing the significance of inhaleability on COPD

Peak inspiratory flow rate (PIFR) is the maximal airflow obtained during inspiration. There are different minimum and optimal PIFR per device used in the treatment for COPD although all devices require enough flow to disaggregate the dose into fine particles. This is significant since like other patients with airflow obstruction, patients with COPD showed a consistent reduction of PIFR likely attributable to air trapping. This reduction is exhibited during an exacerbation and during hospitalization. [Loh CH, et al. Ann Am Thorac Soc. 2017;14:1305-1311. Ghosh S, et al. J Aerosol Med Pulm Drug Deliv 2017;30:381–387]

An ideal inhaler should have the following properties: generation of cloud independent of patient’s inspiration, generation of dose should be during slow inspiration, cloud particles less than 5 µm in size, and low cloud velocity. [Ganderton D. J Aerosol Med. 1999;12:S3–S8.]

“Soft mist inhaler generates a slow moving long-lasting unique mist that helps deliver medication to the patient’s lung with minimal inspiratory effort,” he stated. To maximize dose delivery to the lungs and prevent dose deposition in the oropharynx, the soft mist inhaler (SMI) utilizes three important features: long aerosol duration, reduced aerosol velocity and high fine particle fraction (approximately 75% of the drug dose has cloud particles ≤ 5.8 µm). A longer aerosol duration gives patients time to inhale and helps address the challenge of coordination. Reduced aerosol velocity is more ideal. He emphasized, “the faster [the aerosol velocity], the higher the likelihood of deposition in the oropharynx”. Cloud particles less than 5 µm in size is ideal to maximize dose deposition in the lungs. [Hochrainer D, et al. J Aerosol Med. 2005;18:273–282.; Dalby RN, et al. Med Devices (Auckl). 2011;4:145-155.; Ganderton D. J Aerosol Med. 1999;12:S3–S8.]

However, the treatment strategy for COPD still needs to be individualized for each patient. As Dr Suresca stated, “The goals of COPD treatment are to manage symptoms and reduce the risk of exacerbation. It should include both pharmacological and non-pharmacological approaches including pulmonary rehabilitation and health education.”

Highlighting the COPD Guidelines

“The parasympathetic pathways are the only nerves present in our lungs. A COPD patient would have a narrower airway so if that COPD patient has that tonic tone [as a result of activation of parasympathetic pathway] then that would mean more to him,” Dr Fernandez stated. “Our airways would have a lot of β-2 receptors. So of course, it was very logical that for our patients who are obstructed, then giving our anticholinergics would now lessen the tonic tone and would cause bronchodilation. In the same way, any medications that can stimulate β-2 receptors like β-2 agonist can lead more to bronchodilation,” she continued.

The GOLD 2020 report presented a model for the initiation of the pharmacologic management of COPD. “Long-acting bronchodilators are central to the treatment of COPD, irrespective of exacerbation history. For patients with severe breathlessness, initial therapy with LAMA [Long-acting muscarinic antagonist] / LABA [long-acting β-2 agonist] may be considered,” Dr Suresca summarized. Using LABA/ICS as initial treatment is only considered for patients with moderate to severe exacerbation if their blood eosinophil level ≥ 300 cells/µL. [Global Initiative for Chronic Obstructive Lung Disease. 2020.]

Figure. Initial pharmacological treatment

 

CAT, COPD assessment test; EOS, eosinophil count in cells per microliter; ICS, inhaled corticosteroid; LABA, long-acting β-2 agonist; LAMA, long-acting muscarinic antagonist; mMRC, modified Medical Research Council dyspnea questionnaire.

Adapted from Global Initiative for Chronic Obstructive Lung Disease. Available at: https://goldcopd.org/wp-content/uploads/2019/11/GOLD-2020-REPORT-ver1.0wms.pdf Accessed 16 November 2020.

After treatment initiation, patients are reassessed for symptoms and signs of exacerbation, and identification of difficulties for a successful treatment. Adjustments were performed after review and assessment. “If response to initial treatment is appropriate, maintain it. If not, consider the predominant treatable trait which can either be dyspnea or exacerbation,” Dr Suresca explained. She emphasized that “The management strategy [of COPD] should be predominantly based on the assessment of symptoms and future risks of exacerbations.” [Global Initiative for Chronic Obstructive Lung Disease. 2020.]

“So here brings the question of our use of ICS/LABA in COPD,” Dr Fernandez interjected.

Looking into the role of ICS-containing therapies in COPD

“ICS is not that effective in COPD because of the dominance of neutrophilic inflammation,” Dr Fernandez stated. “The inflammatory cells we are dealing with in COPD are different from asthma. There are more polymorphonuclears, those are the neutrophils, rather than the eosinophils in COPD patients. The thing that we like to use for asthma, that would be our inhaled steroids, would not be that effective in COPD because primarily our neutrophilic inflammation and the CD8 type of T-cell inflammation would not be that steroid responsive,” she explained.

She emphasized that “If you are going to use inhaled steroids among your patients with COPD and they are those in the moderate to severe category, there is a risk of them incurring more pneumonia episodes compared with those who are not given their steroids.”

However, “there is a role for the use of use inhaled steroids for COPD patients and the GOLD guidelines have given practical recommendations for us,” Dr Fernandez stated. The GOLD 2020 report suggest that a history of hospitalization for COPD despite appropriate long-acting bronchodilator maintenance therapy, ≥ 2 moderate exacerbations of COPD per year, blood eosinophils > 300 cells/µL and history of asthma gives a strong support for initiating ICS treatment in combination with LABA. The report also emphasized that ICS should not be initiated if the patient has recurrent pneumonia, blood eosinophils < 100 cell/µL and a history of mycobacterial infection. [Global Initiative for Chronic Obstructive Lung Disease. 2020.]

Conclusion

The treatment strategy for COPD still needs to be individualized for each patient. As Dr Panganiban stated, “A patient can only benefit from a drug that he or she can take properly”. There is also a need for patients to receive the appropriate initial and maintenance treatment. As Dr Fernandez concluded “The name of the game, in terms of treatment for COPD, would still be improvement of airflow obstruction and this is the key approach for COPD treatment.”