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Bob is a 72-year-old male, with a 40-pack-year smoking history. He quit about 8 years ago, when severe COPD was diagnosed. Until last year, he had been stable on his regimen of Advair 250/50 and Spiriva Handihaler, other than an occasional “bronchitis,” usually treated with an antibiotic and/or steroids. Over the past year or so, however, he has noticed a marked turn for the worse. He no longer can walk up the steps in his house without stopping and gasping for breath. He also notes that getting the paper in the morning from the driveway has become a chore, particularly when he bends over. His cough has gotten markedly worse, and is described as hacking and nonproductive.

1. What could be causing the subacute worsening of Bob’s symptoms?

The differential is large, as almost all pulmonary and many non-pulmonary diseases present with the insidious onset of dyspnea and cough. The important teaching point is that patients with COPD, particularly those who had a relatively stable course, may have other etiologies for worsening symptoms than just progression of their COPD. A good clinician will delve into the history more to find a clue.

Bob denies taking up tobacco again. He denies any chest pain. He recently had a cardiac stress test and echocardiogram and was told that the results were unremarkable. He denies any new hobbies or pets. He has travelled to Florida and Europe over the past 2 years. Most of his leisure time now is spent watching television or reading in the house. He denies any new symptoms of arthritis. He notes no mold problems in the home.

 Slightly anxious male, mild respiratory distress

 Numerous actinic keratosis, age-related changes

 Decreased breath sounds, prolonged expiratory phase, crackles at bases

: Normal pulses, +clubbing, no cyanosis, edema

Please click below for next question and discussion. 

2. What are the abnormal findings so far? Does this help us narrow the differential? What should be done next? 

Abnormal findings include the low oxygen saturation, abnormal pulmonary exam including “crackles,” and clubbing noticed in the extremities. Although low oxygen saturation is common in COPD, crackles and clubbing are not signs of this disease. Clubbing can be seen in a number of chronic pulmonary and extrapulmonary diseases-including pulmonary malignancy, interstitial lung disease, bronchiectasis, and inflammatory bowel disease. Probably the most common causes of crackles in the lung acutely are infectious; in a chronic setting, however, crackles should clue you into the possibility congestive heart failure or an interstitial lung disease. 

The primary care physician was concerned about the possibility of interstitial lung disease or pulmonary malignancy. He sent the patient for a high resolution CT of the chest (

Figures 1-3; please click figures to enlarge)

Please click below for Table, Interpretation, Clinical Course, and Diagnosis 

Flows show evidence of moderate obstruction. Lung volumes are normal. Diffusing capacity is very severely reduced. These PFTs, in the absence of additional clinical information, might be interpreted as consistent with COPD. However, the marked reduction of DLCO-which is way out of proportion to the reduction in flows, should clue the clinician into the possibility of a mixed defect. In this patient both the severe emphysema and the pulmonary fibrosis seen on CT scan are negatively affecting the lung’s ability to diffuse CO into the bloodstream, which accounts for the very severe reduction in diffusing capacity. Interestingly, fibrosis and COPD actually counteract each other in flows and volume. Pulmonary fibrosis will actually increase the FEV

/FVC ratio, and COPD will reduce it. Alternatively, pulmonary fibrosis typically reduces lung volumes symmetrically, while COPD can raise TLC and FRC due to hyperinflation. Thus, when patients have combined pulmonary fibrosis and COPD, often lung volumes and flows are relatively preserved, and diffusing capacity is markedly decreased, as seen in this patient. 

The primary care doctor made a tentative diagnosis of pulmonary fibrosis, and referred the patient to a pulmonologist with a special interest in interstitial lung disease. The pulmonologist confirmed the history, and obtained a careful occupational history, toxic drug or exposure history, and sent off screening labs for collagen vascular disease and hypersensitivity pneumonitis. These were essentially negative, other than an ANA that was mildly elevated at 1:40 with a speckled pattern. The patient was discussed in a multidisciplinary conference that included a radiologist, pulmonologists, rheumatologist, and pathologist. 

He was enrolled in a pulmonary rehabilitation program. During his screening 6-minute walk, and also during exercise at rehabilitation, he was noted to have severe oxygen desaturation during exercise to 74%. A portable oxygen concentrator to use at night and with exercise was obtained. Bob was also started on nintedanib, after a careful discussion of the risks/benefits of treatment and alternatives. Over the past 6 months, Bob feels that his symptoms have not significantly changed one way or another. He has had mild diarrhea since starting on nintedanib, but he is able to control it well with occasional use of OTC loperamide.  

IPF is a devastating disease of the lung, causing progressive fibrosis that leads to worsening dyspnea and cough over time. The course can be unpredictable and variable in an individual patient, but on average, patients die from this disease within 3 years of diagnosis. Exacerbations can occur at any time and are particularly ominous, often leading to death within a few months. The disease is predominantly one of the elderly, and men are affected more than women. The cause is unknown, but it is important to rule out other causes of interstitial lung disease, such as collagen vascular disease, medications or toxins, and hypersensitivity pneumonitis. 

Exacerbations can occur at any time and are particularly ominous, often leading to death within a few months. 

Until recently, treatment had been largely supportive. However, in 2015, 2 medications were approved for the treatment of this disease in the United States: pirfenidone and nintedanib. Both medications have been shown to slow the progression of this disease in half, on average. Many trials for new medications are presently underway. Thus, the outlook for treatment and prognosis for this disease is improving, and early diagnosis and referral to an appropriate specialist is important. Many patients like Bob have symptoms for many years before IPF is diagnosed, often in its late stages. Careful attention to patients’ symptoms, physical exam, labs, and radiological studies may help clinicians diagnose this disease earlier and improve the prognosis. 

. Collard HR, Ryerson CJ, Corte TJ, et al. Acute Exacerbation of Idiopathic Pulmonary Fibrosis. An International Working Group Report. 

2016;194(3):265-275.
	. Ley B, Collard HR, King TE Jr. Clinical course and prediction of survival in idiopathic pulmonary fibrosis. 

2011;183(4):431-440.
	. Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. 

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The American Thoracic Society improves global health by advancing research, patient care, and public health in pulmonary disease, critical illness, and sleep disorders.

A Case of Worsening Dyspnea and Cough

Summarized in the slides above are studies presented at the ADA 77th Scientific Sessions that examined treatment regimen effects on glycemic control and variability, including comparisons of:âº Different oral adjuncts to multiple daily insulinâº Different morning insulins, andâº Oral antidiabetic regimens before and after addition of basal insulinÂ Links to meeting abstracts are provided in slide captions.

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Studies summarized in this slide show focus on fine-tuning insulin-containing regimens to enhance glucose control and avoid variability. 

Treatment Strategies to Limit Hypoglycemia 

Among studies presented at at the ADA 77th Scientific Sessions were evaluations of hypoglycemia incidence in large populations, the relation of glycemic variability to risk of hypoglycemia, and glycemic variability as an alternative method to predict hypoglycemia.Three stuides are summarized in the slides above; links to abstracts are provided in the captions.

Glycemic variability fuels hypoglycemia but in one study from ADA 2017 is found to actually help predict hypoglycemic events.  

ADA 2017: Hypoglycemia and the Role of Glycemic Variability 

The cardiovascular safety of antihyperglycemic agents has come under increaesed scrutiny in the last decade with the FDA now requiring manufacturers of newer classes (eg, sodium-glucose-contranposrter-2 [SGLT2] inhibitors) conduct cardiovascular outcome studies as a condition of agency approval. Studies presented at the American Diabetes Association 77th Scientific Sessions last week examined cardiovascular risk profiles of the thiazolidinedione pioglitazone and the SGLT2 inhibitor canagliflozin as well as the 3 gliflozins that make up the SGLT2 inhibitor class.Â Â Trade names for generic drugs mentioned in this slide show appear below:Canagliflozin (Invokana, Janssen)Dapagliflozin (Farxiga, AstraZeneca)Empagliflozin (Jardiance, Lilly)Pioglitazone (Actos, Takeda Pharmaceuticals)Â 

Cardiovascular risk/benefit profiles of pioglitazone and the SGLT2 inhibitor class are summarized, based on reports at ADA 2017.

ADA 2017: Evaluating Cardiovascular Safety of Antidiabetic Agents 

In this selection of Studies at ADA 77th Scientific Sessions included evaluations of whether prediabetes and the criteria used to determine prediabetes, and large weight loss in diabetics may be factors in cardiovascular disease and mortality.

A1C vs FPG to diagnose prediabetes; prediabetes and CHF; and how much weight loss is too much? Reports from ADA 2017. 

ADA 2017: CV Complications of Diabetes 

Studies at the American Diabetes Association (ADA) 77th Scientific Sessions included direct comparisons of a variety of insulin formulations and regimens. Click through the slides above for summaries of 3 studies that evaluate basal insulins in elderly patients; examine the differences between an insulin/oral agent vs insulin only regimen; and report on a cost-benefit analysis of insulin glargine vs insulin degludec -- one costs less because it causes less hypoglycemia.

Insulin degludec vs glargine--which costs less per anum and why? We summarize this study and 2 other direct insulin comparisons reported at ADA 2017. 

ADA 2017: Insulins go Head-to-Head 

During the general poster sessions at the American Diabetes Association (ADA) 77th Scientific Sessions, several of the work-horse oral antihyperglycemic agents were highlighted in studies that looked at B12 deficiency with metformin therapy; adherence with different glimepiride regimens as assessed by an electronic monitoring system; and, the efficacy of a fixed-dose combination vs that of the individual components.

When to start screening for B12 deficiency in your diabetes patients taking metformin? We review a dose-response diet study plus 2 others on oral drugs.  

ADA 2017: Oral Agents Under Review 

In this portion of our Type 2 Diabetes: Back to Basics Special Report, author Dr Susan Williams summarizes the essential principles of T2DM management when diet and lifestyle changes and the addition of 1 or more antihyperglycemic agents have not lowered A1c to the goal set for an individual patient. Included are sections on initiating and intensifying insulin and on precautions to help avoid hypoglycemia.These slides are based on-and incorporate-slides from the AACE/ACE Comprehensive Type 2 Diabetes Management Algorithm 2017 which is available on the AACE website. The algorithm spends equal time on management of T2DM comorbidities/ASCVD risk factors. The presentation summarizes the AACE/ACE 2017 Consensus Statement on comprehensive T2DM management.PLEASE NOTE: TO ENLARGE TABLES ON SLIDES 6, 8, 10, 12, 14, 16, AND 27, PLEASE CLICK ON THE LINK PROVIDED IN THE CAPTION; see example below.[[{"type":"media","view_mode":"media_crop","fid":"59882","attributes":{"alt":"","class":"media-image","height":"289","id":"media_crop_9937304821384","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"7543","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","title":" ","typeof":"foaf:Image","width":"379"}}]]

A how-to overview of how to advance therapy for hyperglycemia and ASCVD risk factors in patients with T2DM.

T2DM: Intensifying Rx When Diet, Lifestyle and OADs Aren't Enough 

The American Association of Clinical Endocrinologists/American Academy of Endocrinology recommend that patients be taught early in treatment how to self-monitor blood glucose (SMBG). Feedback helps patients become aware of the impact of food choices on blood sugar and they tend to be more adherent with treatment plans. For physicians, the patterns revealed by daily recording of SMBG are essential to help fine-tune treatment and specifically insulin therapy. Glucose meter readings plotted for a week will show whether fasting or post-prandial glucose is affecting A1c and direct timing for intensification.Click through these slides for a brief review of the essentials.Content in this portion of Type 2 Diabetes Back to Basics Special Report is based on the AACE/ACEÂ  Clinical Practice Guidelines for Developing a Diabetes Mellitus Comprehensive Care Plan 2015.

Self-monitoring of blood glucose is critical for all patients with T2DM and their physicians.The numbers help modify behavior and Rx. 

Self-monitoring Blood Glucose in T2DM: It's Essential 

We present brief overviews of 7 diabetes apps useful for primary care physicians, including Accurate Insulin Decisions (AID), BMI Calculator by Epocrates, and diabetes management algorithms from the American Diabetes Association and American Association of Clinical Endocrinologists. Also highlighted are 2 comprehensivetracking and education apps you may want to recommend to your patients with type 2 diabetes.Links to the iTunes and Google Play stores can be found in the slide legends.

Seven top diabetes apps for PCPs include insulin calculators, Rx algorithms, comorbidity support, and patient tracking tools.

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