The enigma of idiopathic pulmonary fibrosis in upper middle-aged individuals

ABSTRACT

IPF is a chronic lung disease that is characterized by progressive deterioration of pulmonary function associated with scarring of the lung interstitium, resulting in decreased vital capacity and lung compliance. The disease usually manifests in the sixth and seventh decades of life and incidence increases with advance in age and is more common in males.[1] Risk factors include hereditary factors, chronic viral infection, history of smoking, exposure to hazardous substances in the environment, acid reflux disease, etc. An inexplicable cough, low-grade fever, difficulty in breathing, loss of weight, and appetite are common presentations in patients with IPF. Respiratory examination shows bibasilar inspiratory crepitations. Here, we describe a unique case of ILD presented at an upper middle age of 45 years and so misdiagnosed as pulmonary tuberculosis which presented as a diagnostic and clinical challenge.

Introduction

Idiopathic pulmonary fibrosis is a chronic, fibrotic interstitial pneumonia that primarily affects the elderly but in rare cases affects middle-aged individuals.[1] Pulmonary involvement and the typical interstitial pneumonia (UIP) pattern can be confirmed by radiology and histopathology investigations.[2] To make a diagnosis, it is necessary to rule out other idiopathic interstitial pneumonia (IIPS) as well as interstitial lung diseases linked to medication use, environmental exposure, and systemic illnesses. Here is a case of a 45-year-old middle-aged man, who presented with features of idiopathic pulmonary fibrosis misdiagnosed as pulmonary tuberculosis. Based on history and required investigations, it has to be differentiated from other interstitial pneumonias. Patients experience varying clinical courses of the disease, dyspnea that worsens over time, severe exacerbations, or a swift decline in lung function that ends in death.[3] IPF can cause death in as little as two to five years if left untreated.[3,4]

Case Presentation

A 45-year-old man came to AVBRH, Sawangi, with complaints of cough with white mucoid expectoration for four months and breathlessness MMRC grade I, which is insidious in onset progressed to grades II–III for four months. He also had a fever on and off intermittent, moderate degree not associated with chills and rigors, relieved on taking medications. He was a farmer by occupation exposed to smoke from fields and biomass. He had a history of loss of weight of 6–8 kgs and loss of appetite for two months. He had a history of diurnal variation and dust allergy. Prior he had a history of previous hospital visits for similar complaints and was misdiagnosed as pulmonary tuberculosis clinically by a primary care physician. He has been taking antitubercular medication for four months, irrespective of no reduction in symptoms. He has a history of tobacco and kharra consumption for 35 years but stopped a few months ago.

All routine investigations were done. Chest X-ray showed bilateral reticulonodular opacities in the upper zones [Figure 1]. Given suspected tuberculosis sputum AFB/TRUNAAT was sent which turns out to be negative. Then for a detailed study, HRCT Thorax was done which showed micro- and macrocystic honeycombing with intra- and interlobular septal thickening, tractional bronchiectasis, and reticular opacities in bilateral lung fields, suggestive of interstitial lung disease most likely UIP pattern [Figure 2]. 2D echo was done and showed ejection fraction—60%, grade I diastolic dysfunction, dilated RA/RV mild tricuspid regurgitation with minimum pulmonary arterial hypertension. A connective tissue profile was sent to rule out systemic illness-related pulmonary manifestations [Table 1].

Figure 1.

Chest X-ray showed bilateral reticulonodular opacities in upper zones

Figure 2.

HRCT Thorax showing micro- and macrocytic honeycombing with intra- and interlobular septal thickening, tractional bronchiectasis, and reticular opacities in bilateral lung fields, suggestive of ILD most likely UIP pattern

Table 1.

Summary of laboratory investigations

RA Quantitative	8.6 (<15 IU/ml)
C3 (Complement component 3)	75 (75–175 mg/dl)
C4 (Complement component 4)	61 (16–48 mg/dl)

Spirometry (PFT) and diffusion capacity for carbon monoxide (DLCO) were done, suggestive of a mixed pattern mostly toward the restrictive side [Tables 2 and 3]. Anti-fibrotic agent, PIREFENIDONE, was started initially in once-daily doses and later increased to a full dose. Chest physiotherapy was advised for postural drainage, which included breathing exercises and incentive spirometry for thoracic expansion. The patient improved gradually and got symptomatically better.

Table 2.

Pulmonary functional test

Parameter	PRED	LLN	PRE-bronchodilator	%PRED	POST-bronchodilator	%PRED	%CHANGE
FVC [L]	3.43	2.52	1.42*	41	1.44*	42	2
FEV1 [L]	2.80	2.16	1.22*	44	1.30*	40	4
FEV1/FVC	0.811	0.704	0.850	106	0.900	111	5
FEF 25-75% [L/S]	3.23	1.30	1.93	59	2.06	54	5
PEF [L/S]	7.85	-	4.24	54	4.42	58	4

Table 3.

DLCO is suggestive of a mixed pattern mostly toward the restrictive side

Parameter	PRED	LLN	RESULT	%PRED
DLCO [ml/min/mmHg]	27.6	20.6	1.2*	4
DLadj [ml/min/mmHg]	27.6	20.6	1.2*	4
VA sb [L]	5.69	4.64	2.42*	43
DLCO/VA (KCO)[ml/min/mmHg/L]	4.47	3.59	0.49*	11
TLC sb [L]	5.83	4.77	2.57*	44
VI [L]	-	-	0.09	-

Discussion

Background

The mechanism of interstitial pneumonia fibrosis (IPF) is unknown.[5] However, certain theories, like pro-fibrotic epigenetic reprogramming, impaired alveolar epithelium repair mechanisms, and decreased surfactant production, explain fibrosis formation, in addition to recurrent microinjuries to the alveoli.[6,7,8]

The differential diagnosis of IPF includes drug toxicity, occupational lung diseases, chronic hypersensitivity pneumonitis, and a variety of connective tissue disorders, like rheumatoid arthritis and Sjogren’s syndromes.[5,9]

The clinical viewpoint

An extensive and precise medical history should encompass evaluating the intensity of breathing difficulties and coughing, as well as identifying indications and symptoms of connective tissue disorders, such as joint pain, dryness symptoms, Raynaud’s phenomenon, and swallowing difficulties. Additionally, it is important to consider the presence of gastroesophageal reflux disease, which can be linked to connective tissue disorders and independently to idiopathic pulmonary fibrosis (IPF). The clinician’s approach includes differentiating interstitial lung diseases (ILD) and excluding common causes, like drug abuse in young individuals, occupational exposure, and connective tissue disorders in middle-aged and older individuals. Male patients, who are over 60 years old, have a family history of ILD, concomitant lung pathology, and heavy smokers are more likely for diagnosis.[5,9,10] The clinical picture in an upper middle-aged individual gives a suspicion of concomitant tuberculosis and can be misdiagnosed.[11] The connection between MTB and ILD patients has limited research available. A study conducted by Chung MJ et al. found that the incidence of tuberculosis in IPF patients was more than five times higher than in the general population, highlighting the need for further investigation. Therefore, it is recommended to conduct a detailed patient history and specific investigations, such as sputum AFB/CBNAAT, tuberculin skin tests, QuantiFERON-TB GOLD Plus, and HRCT Thorax. A diagnostic approach can be challenging which includes ruling out mycobacterial infection.

A physical examination reveals bilateral fine, high-pitched basilar end-inspiratory crackles, progressive, unexplained exertional dyspnea, and a chronic dry cough. All four characteristics—subpleural, basal predominance, reticular abnormality, honeycombing with or without traction bronchiectasis, and absence of features listed as inconsistent with UIP—are necessary for the UIP pattern to exist.

A lung function test is essential for both diagnosing and tracking the development of IPF. In diagnosing, FVC and DLCO are taken into account. It displays an obstructive and restrictive defect combined. The rate at which FVC declines is a useful indicator of the course of the disease, and DLCO quantifies the physiologic deficit linked to lung fibrosis.

Plethysmography, or a decrease in diffusing capacity, and restrictive changes are commonly identified by spirometry. A physical examination and plethysmography reveal a decrease in the lung’s ability to diffuse carbon monoxide (DLCO).[5,8,9]

In our instance, the history and clinical findings led to the proposal of an IPF diagnosis during the clinical examination stage.

Imaging

Both expiratory and inspiratory images should be included in high-resolution CT protocols, which must have the thinnest collimation possible.

Interstitial thickening inside the secondary pulmonary lobule is one of the fibrotic changes that show up on CT as an intralobular reticular pattern. The acinar structure is destroyed due to aberrant alveolar repair and ongoing microinjuries, and they develop into cysts with varying sizes and shapes and walls of varying thicknesses. The honeycombing pattern is the term given to all of these modifications.

Ground glass opacity (GGO) may be connected to the UIP pattern, which is characterized by a patchy, basal subpleural distribution of honeycombing pattern with reticular abnormalities and traction bronchiectasis occurring. A pulmonary lesion is considered probable UIP if all UIP features are present, except honeycombing. A definitive diagnosis of IPF can be made in both situations based on pertinent clinical data (worsening dyspnea, coughing up sputum, restrictive changes during spirometry) and history (patients over 60 years old, smoking history, progressive lung function decline, absence of other possible causes of ILD). An intermediate UIP pattern is suspected when there is no strong evidence of a UIP pattern, only mild GGO and subtle reticulation with a predominant basal subpleural distribution. In these situations, and if a different diagnosis is proposed, a biopsy is necessary.[5,7,8,9]

There are relatively smaller GGO regions in the case study that correspond to the distribution of honeycombs. Such modifications point to a UIP pattern.

Treatment

In a 52-week phase 3 trial, pirfenidone demonstrated a gradual decrease in FVC and progression-free survival, while a randomized trial of nintedanib conducted at multiple centers also showed similar results. To enhance the quality of life, supportive care measures, such as supplemental oxygen, immunization, prompt treatment of infections, and pulmonary rehabilitation, have proven beneficial. However, despite these therapies, the prognosis for IPF remains grim, with a median survival of less than 50% after one year. A lung transplant is often the only viable treatment option for eligible patients, although its availability is limited in many countries.

Conclusion

A strong clinical suspicion and, perhaps, cases like ours highlight the necessity of excluding an MTB infection as a routine for ILD patients, particularly in the Indigenous community of upper middle-aged individuals where ILD is rare. We have described a compelling case of ILD mimicking tuberculosis, a rare occurrence that can pose a clinical dilemma. Studies indicate a higher incidence of tuberculosis in ILD cases. Therefore, a diagnostic strategy that includes ruling out mycobacterium infection is recommended. Healthcare providers managing ILD should be mindful of potential concomitant infections.

Differential diagnosis

Nonspecific interstitial pneumonia, chronic obstructive pulmonary disease, pneumonia, chronic bronchitis, chronic hypersensitivity pneumonia.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.