Most Common Cause Of Pneumonia In Diabetes – Salim Surani, MD, MPH, NSHM, FACP, FCCP, Professor, Department of Pulmonary Critical Care and Sleep Medicine, Texas A&M Health Science Center, 8441 Riverside Pkwy, Bryan, TX 77807, United States. [email protected]

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Most Common Cause Of Pneumonia In Diabetes

Most Common Cause Of Pneumonia In Diabetes

Salim Surani, Department of Pulmonary Critical Care and Sleep Medicine, Texas A&M Health Science Center, Bryan, TX 77807, United States

Community Acquired Pneumonia In Adults: Diagnosis And Management

Author Contributions: All authors contributed to manuscript preparation, literature search, and manuscript review.

Open Access: This article is an open access article selected by an internal editor and fully reviewed by external reviewers. Distributed under the Creative Commons Attribution NonCommercial License (CC BY-NC 4.0), which allows others to distribute, remix, adapt, build on this work non-commercially, and license their derivative works under different terms; provided the original work is properly attributed and the use is non-commercial. I see:

Corresponding author: Salim Surani, MD, MPH, NSHM, FACP, FCCP, Professor, Department of Pulmonary Critical Care and Sleep Medicine, Texas A&M Health Science Center, 8441 Riverside Pkwy, Bryan, TX 77807, United States.

Diabetes mellitus (DM) is a chronic metabolic disease and its prevalence is steadily increasing worldwide. DM and its associated micro- and macrovascular complications result in significant morbidity and mortality. Microvascular complications usually manifest as retinopathy, neuropathy, nephropathy, and macrovascular complications generally affect the cardiovascular system. In addition to these complications, DM also affects the lungs due to its rich vascularity and abundance of connective tissue (collagen and elastin). DM has been found to cause microvascular complications and proliferation of extracellular connective tissue in the lungs, leading to a decline in lung function in a restrictive pattern. Interstitial lung disease (ILD) comprises a diverse group of diseases characterized by varying degrees of inflammation and fibrosis in the lung parenchyma. Idiopathic pulmonary fibrosis (IPF) is one of the common types of idiopathic interstitial pneumonia with a high mortality rate. IPF is characterized by chronic progressive fibrosis leading to progressive respiratory failure. In this review we focus on the lung as the target organ in ED and the association of ED and IEF with particular emphasis on IPF.

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Key words: Diabetes mellitus, Interstitial lung disease, Idiopathic pulmonary fibrosis, Metformin, Complications of diabetes, Pulmonary function test, Restrictive lung disease, Hyperglycemia

Key tip: Diabetes mellitus is a common chronic disease with high prevalence leading to multiple complications and comorbidities. Diabetic lung disease or diabetic lung disease is a condition characterized by progressive lung disease caused by microvascular complications associated with diabetes mellitus. Early recognition of this complication and tight control of blood sugar in patients with diabetes can prevent the progression and debilitating symptoms associated with diabetic lung.

Diabetes mellitus (DM) is not only a common chronic disease but also a global health problem that has expanded significantly in recent decades. The World Health Organization reported that the number of people with DM has increased from 108 million in 1980 to 422 million, and 8.5% of the global adult population had DM in 2014[1]. The number of diabetic patients worldwide has been estimated to reach 592 million in 2035 by the International Diabetes Federation[2]. DM is characterized by hyperglycemia, which is secondary to insulin deficiency, which can be relative or absolute. Over 50% of DM patients are unaware of their diagnosis and are at risk of developing complications. It causes microvascular and macrovascular complications. Microvascular complications generally manifest as nephropathy and retinopathy. Macrovascular complications include coronary heart disease, cerebrovascular disease, and peripheral arterial disease[3]. In addition to these complications, pulmonary complications including decreased lung function as well as pulmonary fibrosis have been reported in the literature[4]. The pulmonary system is prone to microvascular damage and non-enzymatic glycosylation due to its large vascular bed and the presence of abundant connective tissue. Our review will mainly focus on the lung as a target organ for DM and the association between DM and interstitial lung disease (ILD).

Most Common Cause Of Pneumonia In Diabetes

The pathogenesis of DM leading to interstitial lung disease is multifactorial and highly complex (Figure 1)[5]. Hyperglycemia leads to oxidative stress and causes an imbalance between free radical generation and antioxidant activity and this contributes to lung dysfunction in DM. Diabetes often when poorly controlled leads to autonomic neuropathy that can affect pulmonary vascular tone resulting in pulmonary hypertension and phrenic nerve neuropathy that can lead to diaphragmatic dysfunction and these patients usually present with unexplained dyspnea and orthopnea. Autonomic neuropathy also affects pulmonary mechanoreceptors resulting in impaired airway smooth muscle tone and excessive surfactant production [6]. Long-term hyperglycemia leads to nonenzymatic glycosylation of extracellular proteins in the pulmonary interstitium, contributing to ILD in DM. DM-induced pulmonary capillary microangiopathy together with glycosylation of alveolar basement membrane proteins results in significant impairment of alveolar gas exchange[7].

Community Acquired Pneumonia Requiring Hospitalization Among U.s. Adults

Figure 1 Pathophysiology of diabetic lung disease. FEV1: Forced expiratory volume in 1 s. FVC: Forced Vital Capacity. DLCO: Diffusing capacity of the lungs for carbon monoxide.

There is considerable evidence that the incidence of IPF increases with age and therefore it is possible that age and lifestyle-related diseases including DM could be a risk factor for the development of IPF. It is also interesting to note that another possible link between IPF and DM is gastroesophageal reflux disease (GERD). Patients with DM are at higher risk of GERD, and studies suggest that GERD is an important risk factor for IPI due to its association with microaspiration[8]. There have been many studies that have reported an accelerated decline in lung function in patients with DM and poor glycemic control. The microvascular complications associated with diabetes also lead to pulmonary capillary basal lamina thickening, reduced pulmonary capillary blood volume, autonomic nervous system dysfunction, connective tissue matrix glycosylation, and oxidative stress resulting in a significant reduction in the diffusive capacity of the lung[ 9].

DM also leads to pulmonary autonomic neuropathy which affects ventilatory control with reduced ventilatory response to hypoxia but not hypercapnia[10]. Dysfunction of parasympathetic tone leads to an increase in airway caliber, reduced mucosal clearance, and increased susceptibility to pulmonary infections[11]. Defective muscle metabolism leads to a decrease in muscle strength. Respiratory muscle endurance decreases and is inversely proportional to hemoglobin A1c. DM leading to phrenic nerve neuropathy impairs respiratory neuromuscular function and leads to decreased lung volume and accelerates restrictive complications in diabetic patients[12]. Because of the large pulmonary reserve, micro- and macrovascular dysfunctions due to DM develop later in the lungs than in other organs. Oxidative stress, endothelial microinjuries and platelet activation with sequential inflammation are considered important mechanisms in the development of pulmonary fibrosis[13].

Studies have suggested two main mechanisms by which diabetes leads to lung disease. The thorax and lungs are rich in collagen and elastin, and nonenzymatic glycosylation of these compounds could lead to stiffness of the thoracic cage and lung parenchymal tissue resulting in a restrictive physiology. The second mechanism by which DM causes lung damage is through pulmonary microvascular damage that runs parallel to nephropathy, retinopathy, and neuropathy. This results in thickening of the alveolar epithelium and basal laminae of the pulmonary capillaries and reduced presence of pulmonary capillary blood volume[14]. The combination of alveolar wall thickening and reduced perfusion leads to a blood-ventilation mismatch resulting in reduced diffusion capacity.

Precipitating Causes Of Diabetic Ketoacidosis And Hyper Glycemic…

It is interesting to note that both international guidelines for ILD and DM do not mention DM as a risk factor for ILD. A German study examined 280 participants (18 to 75 years) in outpatient clinics to investigate the incidence of restrictive lung disease and ILD in patients with prediabetes and type 2 DM[ 15 ]. This study included 48 non-diabetics, 68 prediabetes, 29 newly diagnosed type 2 DM patients, and 110 long-term type 2 DM patients. Five participants with type 2 DM, dyspnea, and restrictive lung disease underwent high-resolution computed tomography (CT) and 6-minute walk test. Of the 5, ILD was diagnosed in four patients and histological analysis revealed fibrous ILD[15]. 9% of patients who were prediabetic had restrictive lung disease, while it was seen in 20% and 27% of newly diagnosed and long-standing DM, respectively. In patients with long-term diabetes, the presence of albuminuria, nephropathy were independent risk factors for the development of restrictive lung disease. The MMRC (Modified Medical Research Council) dyspnea scale showed increased dyspnea in patients with long-standing type 2 DM compared to prediabetic and non-diabetic patients. Elevated fasting glucose was significantly associated with decreased forced vital capacity (FVC). Normal lung tissue obtained from patients during surgery for lung cancer (3 with and 4 without diabetes) showed increased fibrotic disease in patients with type 2 DM compared to non-diabetics. This study showed an increased risk for shortness of breath and

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